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Kegawatan Hematologis Pada Neonatus Kritis - DR Azharry, SpA
Kegawatan Hematologis Pada Neonatus Kritis - DR Azharry, SpA
Muhammad Azharry R.
Hematology Emergency
Bleeding Thrombosis
• Anemia • Causes
• Coagulation disorders • Evaluation
• Transfusion and non- • Management
transfusion management
Bleeding
ANEMIA
in Neonates
Formation Process of RBC
The formation process of RBC since intrauterine
Zivot A et al. Erythropoiesis: insights into pathophysiology and treatments in 2017. Mol Med. 2018;24:11
Bernard G Forget. Progress in understanding the hemoglobin switch. N Engl J Med. 2011;365:853-4
Zivot A et al. Erythropoiesis: insights into pathophysiology and treatments in 2017. Mol Med. 2018;24:11
The shorter lifespan of RBC, the easier it is to lyse (physiological) ->
higher dan faster risk of hyperbilirubinemia
Kuruvila et al. Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities. Pediatr Res.2017;81:905-10.
Definition
COAGULATION
DISORDERS
in Neonates
Blood Clotting Process
Involving:
• Blood vessel Blood clots
(temporary)
• Platelets
• Coagulation factor and
fibrinolytic enzyme Blood clots
(permanent)
• Tissue
Primary Hemostasis Secondary Hemostasis
1o 2o
Vasoconstriction, aggregation, and Activation of coagulation system →
platelet deposition fibrin plug which stabilizes the platelet
→ platelet plug plug
PT & PTTValue
Normal Reference Value
of Platelets
Reference for Normal Value of Coagulation J Perinatol Off J Calif Perinat Assoc. 2009 Feb;29(2):130–6.
Factors in the First 6 Months of Term Babies Front Pediatr. 2021 Mar 2;9:627715.
Br J Haematol. 2002 Nov;119(2):295–309.
BLEEDING BLEEDING
Intervention
Intervention
Stops
Continues
Re-bleeding
Prolonged bleeding
(Delayed bleeding)
Platelet disorders
1o Coagulation factors
20
Spontaneous Bleeding
(Without Trauma)
Who
Step 1 • Age,
Are gender,
there familyabnormalities?
any platelet history of bleeding, healthy/sick baby
DPL and peripheral blood
Thrombocytopenia or disfunction smear
Bleeding time
• Bleeding onset, bleeding clinical history, comorbidities, trauma history (at
When
Step 2 birth)
Are thereor surgery,
any medication
coagulation factorsusage in pregnancy
deficiency? PT,or infant period (giving
APTT
vitamin
Factor K atIX,
VII, VIII, birth?)
X, V, XI, Fibrinogen
TRANSFUSION &
NON-TRANSFUSION
MANAGEMENT
Management of Anemia
Principles of
Management
• Adequate oxygenation
(according to cardiorespiratory
clinical manifestation)
• Adequate nutrition and fluid
• Selective RBC transfusion
(top-up)
• Supplementation (if indicated)
Blood Transfusion
The process of administering blood or blood components from one person to another
Benefit
• life saving
• Improve oxygenation & homeostasis
• return blood volume
Risk
• Infection transmission
• Acute/delayed reaction
Sahu S, Hemlata, Verma A. Adverse events related to blood transfusion. Indian J Anaesth. 2014;58(5):543–51.
Blood Product Transfusion
Whole
blood
Transfusion
Fresh
Cryoprecipit
Frozen
ate
Plasma
RBC Transfusion
RBC Transfusion Indications
Clinical symptoms of anemia
Clarke G, Charge S. Clinical guide to transfusion medicine. Canadian Blood Services; 2019
RBC Transfusion
Liberal Restrictive
• Transfusion is carried out if • Transfusion is carried out
Hemoglobin is ≤10 g/dL if Hemoglobin is ≤6 g/dL
• Hemoglobin target is ≥11 • Hemoglobin target is ≥8-
g/dL 10 g/dL
Clarke G, Charge S. Clinical guide to transfusion medicine. Canadian Blood Services; 2019
Hemoglobin
Hemoglobin ConcentrationLimits
HematocritConcentration
Concentration Limitsfor
Limits
for Giving
Giving
forPRC PRC Transfusion
Transfusion
Giving PRC (Term)
(Premature)
Transfusion
Condition Hb (g/dL)
Operation <10
Neonatology 2021;114:7–16
KirpalaniH, Whyte RK, J Pediatr2020; 149: 301-7.
Whole Blood vs PRC Transfusion
• Advantages:
• Suitable for acute bleeding conditions BW (kg) x Hb
Whole • Easy to prepare increase target
Blood • Disadvantages: (g/dL) x 6
• Risk of overload because the volume is greater than PRC
• Advantages:
• Smaller volume BW (kg) x Hb
PRC • Contains less plasma increase target
• Disadvantages: (g/dL) x 4
• Contains much less coagulation factors than WB
Clarke G, Charge S. Clinical guide to transfusion medicine. Canadian Blood Services; 2019
Platelet Transfusion
Platelet Transfusion Indications
• Thrombocytopenia with or without clinical symptoms of
bleeding
• Prophylaxis
Transfusion of platelet concentrate as prophylaxis of
bleeding is not recommended
New HV. Guidelines on transfusion for fetuses, neonates and older children. British Committee for Standards in Hematology; 2019.
Limits for Platelet Transfusion
Administration
Conditions Platelets (mm3)
Term neonates, without bleeding <30.000
Preterm neonates, without bleeding <25.000
• With bleeding, clinically unstable 30.000-50.000
• BW <1000 g
• IVH grade III/IV
• Coagulopathy
• Surgery (<72 hours)
Curley A, Stanworth SJ, Willoughby K. RCT Platelet-Transfusion Thresholds in Neonates. N Engl J Med. 2021.
Coagulation Factors Transfusion
Limit Values for Coagulation Factors
Transfusion
Joint United Kingdom (UK) Blood Transfusion (2021). Neonatal Transfusion guidelines.
Fresh Frozen Plasma (FFP)
• Each unit (200-250 mL)
• All coagulation factors, include
• FVIII (0.6 IU/mL)
• FIX (0.9 IU/mL)
• Fibrinogen 250-300 mg
• Albumin, globulin, protein C, & protein S
Indication
1. APCD
2. DIC with active bleeding
3. Hepatic dysfunction with active bleeding
Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee (2019). Neonatal Transfusion guidelines. [online] Transfusionguidelines.org.
Cryoprecipitate
Indication:
• von Willebrand disease, F VIII Def (hemofilia
A) or F XIII Def
• fibrinogen def. with active bleeding, invasife
procedure, trauma, DIC
Massive transfusion
• Blood loss of >40% of the total blood
volume (i.e. >30ml/kg) is immediately
life-threatening.
Delayed
reaction
Acute reaction >24 hours – 30
days
Occurs
immediately or
<24 hours
Reactions that
occur due to
transfusion
administration and
its components
Josephson CD. Neonatal and pediatric transfusion practice. In: Roback JD, Combs MR, Grossman BJ. 2022.
Transfusion-Related Adverse
Reactions
• Medication error:
• Blood product type error
• Recipient identity error
• Immunological reaction
• Non-immunological
reaction
J Pediatr 2011;158:403–409.
Basavarajegowda A, Plakkal N. Transfusion reactions in neonates and pediatrics: How and why are they different? Asian J Transfus Sci 2023;17:97-102
Transfusion-Related Adverse
Reactions in Neonates
Because the immunity is still immature, reactions like fever or allergy occur
less frequently
Transfusion-Related Adverse
Reactions in Neonates
Impaired BS stability due to low glycogen and mucosal G-6-
phosphatase reserves
Transfusion Reaction Management
Delaney M et al. Transfusion reactions: prevention, diagnosis, and treatment. The Lancet. 2016;388:2825–36.
Management of Bleeding
• If the bleeding is active, apply a splint
• In case of 2o hemostasis, consider doing RICE
→Rest-Ice (cold)-Compress-Elevation
• In special cases
• Vitamin K administration
• Prothrombin complex consentrate
Munlemwo DM, et.al. Prothrombin Complex Concentrates to Treat Coagulation Disturbances: An Overview With a Focus on Use n Infants and Children. Cardiol Res. 2022;13(1):18-26.
Tranexamic acid
THROMBOSIS
in Neonates
Causes
Developing coagulation system, need for intensive care (including catheterization),
and comorbid conditions are responsible for the high risk of thrombosis in neonates
compared to older children
Bhatt MD, Chan AKC. Venous thrombosis in neonates. Faculty Reviews. 2021;10:(20).
Management
Unfraction
ated
heparin
(UFH)
Anti-
coagulant
drugs
Oral Low-
molecular-
vitamin K
weight
antagonis heparin
ts (VKA) (LMWH)
Monagle P, Newall F. Management of thrombosis in children and neonates: practical use of anticoagulants in children. American Society of Hematology. 2018;1:399-404.
Unfractionated Heparin (UFH)
Advantages:
• Short half-life
• Rapid onset and offset of action
• Ideal for cardiopulmonary bypass, circuit prophylaxis, procedural prophylaxis (ex. Cardiac
catheterization), and maintaining vascular access patency
Monagle P, Newall F. Management of thrombosis in children and neonates: practical use of anticoagulants in children. American Society of Hematology. 2018;1:399-404.
Unfractionated Heparin (UFH)
Maintenance UFH doses are age dependent
• Infants (up to 2 months) → 28 U/kg/hour
• Older than 1 year old → 20 U/kg/hour
• Older children → 18 U/kg/hour
Potential side effects:
• Bleeding
• Anaphylaxis
• Osteoporosis
Monagle P, Newall F. Management of thrombosis in children and neonates: practical use of anticoagulants in children. American Society of Hematology. 2018;1:399-404.
Case thrombosis post central line insertion
Thank you