Approach To Bleeding Disorders In Neonates هو الشّافی Approach To Bleeding Disorders In Neonates S.A.Afjeh (MD) SBUMS MMC 1396

I) Introduction Bleeding in well baby is rare BUT in sick baby is serious Clinical Presentation : ICH, Cephalhematoma, Venipuncture, Bruising, GIB, … Etiology : Congenital or Acquired Coagulation Systems : Cellular (Platelets, …) Plasma Proteins (Developmental Hemostasis) Ref : Blood Coagul Fibrinolysis 2011;22:110e7.

II) Fetal development of the coagulation system Ref : Pediatr Clin N Am 2013; 60:1407e17.

III) Congenital Hemophilia Type A & B (F VIII & F IX) X Link Recessive Incidence 1/5000 - 1/200000, Male Classification : Severe (< 1%), Moderate (1-5%), Mild(>5-40%) Circumcision, ICH (Assisted Vaginal Delivery) Mean Age : 28.5 days, First Month : 70% F VIII activity in neonates as normal adults but F IX activity is about 50% of adult level at birth Treatment : Factor Concentration Ref : Am J Hematol 1998;59:288e94.

III) Congenital Von Willebrand Disease (VWD) Most frequent inherited bleeding disorder Mucocutaneous & Gum bleeding, Epistaxis, GIB, Bruising Autosomal Recessive & Dominant, 1% population Types : 1 (Partial Quantitative Deficiency, Most Common), 2 (Qualitative, Severe Bleeding), 3 (Complete Deficiency, Most Severe Bleeding, Rarest) Diagnosis Quantitative VWF in plasma Quality VWF & ability to bind platelet Factor VIII activity VWF is normal or high at birth RX : pd.F VIII Ref : Hematology Am Soc Hematol Educ Program 2012;2012:161e7.

III) Congenital Rare Inherited Bleeding Disorder Fibrinogen Disorders Hypofibrinogenemia (Heterozygous) or afibrinogenemia (Aut.R) or dysfibrinogenemia Prolong umbilical bleeding, post circumcision, ICH, … Diagnosis : Prolong PT, aPTT, Decreased functional or antigen fibrinogen assay Treatment : Fibrinogen concentrates, FFP, Cryopercipitate Ref : Haemophilia 2008;14:1151e8.

III) Congenital Rare Inherited Bleeding Disorder Prothrombin (F II), F V, F VII, F X, F XI Deficiency Autosomal Recessive Mucocutaineous Bleeding, Trauma, ICH, Umbilical Bleeding F VII & XI levels do not correlate with bleeding phenotype Diagnosis : ↑PT & aPTT (F II, F V, F X), Isolated ↑PT (F VII) & ↑aPTT (F XI), Specific Factor Assay Treatment : Factor Concentrate F VII (rF VIIa) F II, F VII, F IX, F X (Prothrombin Complex Concentrate) FFP (F V & XI) F XI in some countries Ref : J Thromb Haemost 2009;7(Suppl. 1):84e7.

III) Congenital Rare Inherited Bleeding Disorder F XIII Deficiency Autosomal Recessive, Subtype A & B Umbilical Bleeding (50-70%), Bleeding After Procedure or Trauma Diagnosis : PT, aPTT, Qualitative F XIII assay, Clot solubility assay (Not sensitive for low level F XIII) Treatment : pd F XIII, Recombinant F XIII, Cryoprecipitate (If F XIII concentrate is not available) Ref : J Thromb Haemost 2003;1:1852e3.

IV) Acquired Liver Failure Synthesis of most pro & anti coagulant proteins (Except F VIII & VWF) in liver Bleeding & Thrombosis Elevated PT, aPTT, D-dimer Decreased fibrinogen activity & platelet count Treatment : FFP, rF VIIa, Cryopercipitate Ref: Pediatric Blood Cancer 2009;53:179e83.

IV) Acquired Vitamin K Deficiency Platelet dysfunction or thrombocytopenia DIC Therapeutic Hypothermia (Total Body or Head Cooling) Treatment for HIE Increased Risk of ICH, CBF, ↓ BP, Platelet & Coagulation System Function Coagulopathy, Thrombocytopenia, Bleeding Treatment : FFP, Cryopercipitate Ref: N Engl J Med 2009;361:1349e58.

V) Algorithm for the approach to a bleeding neonate Ref: Seminars in Fetal & Neonatal Medicine 21 (2016) 44e49.

VI) Conclusion Neonates are in a continuous state of developmental hemostasis. Bleeding in neonates can be challenging to diagnose and treat. With systematic evaluation of various coagulation tests, the appropriate diagnosis can be made and treatment can be initiated. Initially, treatment is often supportive, but once a diagnosis is made, it can and should be tailored to specific etiologies.

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