Bleeding neonate

Dr.Sandip GuptaPGT,PEDIATRICS

B.S.M.C.H.

Introduction

• Neonates are susceptible to bleeding for various reasons

· Immaturity of the haemostatic system because of quantitative and qualitative deficiency of coagulation factors

· Maternal disease and drugs · Birth trauma · Other conditions - sepsis and asphyxia

Clinical presentation

• Bleeding in neonates may present with· Oozing from the umbilical stump · Cephalhaematoma · Bruising , Petechiae · Bleeding from peripheral

venipuncture or procedure sites · Bleeding following circumcision · Intracranial haemorrhage · Bleeding from mucous membranes · Unexplained anemia and hypotension

Etiology

A.Deficiency of clotting factors:1.Transitory deficiencies-Deficiency of vitamin K dependent

C.F- II, VII, IX, X. Deficiency of anticoagulant proteins

C & S.

Causes:a. Total parenteral nutrition or antibioticsb. Lack of administration of vitamin K .c. Drug intake in pregnancy eg.i. Phenytoin, Phenobarbital, Salicylates . (Interferes with the synthesis of vit. K

dependent c.f. ) ii. Calmodulin compounds

• The incidence among babies born to mothers on these drugs have varied between 6-12%*.

In a recent series on children born to mothers on anticonvulsants, abnormal PT was documented in 14 out of 105 babies (13%) , no overt bleeding was observed*.

2. Disturbances of clotting- Related to DIC due to infection, shock,

anoxia, NEC, renal vein thrombosis, use of IV canula.

3. Inherited abnormalities of C.F. a. X-Linked recessive diseases- i. Hemophilia-A : Factor VIII deficiency. ii. Hemophilia-B : Factor IX deficiency.

b. Autosomal dominant diseases: i. Von Willebrand disease – Deficiency of

VWF which is a carrier of factor VIII & as a platelet aggregation agent.

c. Autosomal recessive diseases: i. Severe factor VII & factor XIII deficiency –

intracranial hemorrhage in neonates ii. Factor XI deficiency – unpredictable bleeding during

surgery/trauma.

iii. VWD Type III

B. Platelet problems:1. Qualitative disorders:- Glanzman’s thrombasthenia.- Bernard-Soulier syndrome- Platelet type VWD

2. Quantitive disorders:- Immune thrombocytopenia- Matrnal Preeclampsia, HELLP syndrome

or severe uteroplacental insuffuciency.- DIC due to infection or asphyxia.- Inherited marrow failure syndromes :

Fanconi anemia & congenital amegakaryocytic thrombocytopenia

- Congenital leukemia- Inherited thrombocytopenia

syndromes : gray platelet syndrome- Macrothrombocytopenias : May-Hegglin

syndr.- Platelet consumption in clots/ vascular

disorders eg. Vascular malformations, NEC.

C. Vascular origin:- Pulmonary haemorrhage- A-V malformations- CNS haemorrhage- Hemangiomas.

Diagnostic workup

• HISTORY: A detailed history and examination essential in the assessment of bleeding neonate

History includes

• Maternal diseases as ITP, preeclampsia .

• Maternal exposure to drugs as aspirin, anticonvulsants, rifampicin and isoniazid

• Family history of bleeding disorders

• Previous affected sibling

B. Examination:First diagnose whether the infant is Sick or Well1. Sick infant: - DIC - Bacterial/ viral infections.2. Well infant:- Vit K deficiency- Isolated C.F. deficiencies- Immune thrombocytopenia- Maternal blood in infant’s GIT.

3. Patchiae, ecchymosis, mucosal bleeding: Platelet problem

4. Large bruises: DIC, C.F deficiencies, liver diseases

5. Enlarged spleen : Possible congenital infections or erythroblastosis.

6. Jaundice : Sepsis, liver diseases, resorption of large hematoma.

C. Laboratory tests: 1. Apt test : - To rule out maternal blood in infant’s

GIT - Done in otherwise well infant with only

GI bleeding.2. PBS : - DIC- fragmented RBCs - Congenital macrothrombocytopenias –

large platelets.

3. PT 4. APTT 5. D-Dimer assays: Measure fibrin

degradation products in DIC & Liver diseases causing defective clearing of fibrin split products.

6. Specific factor assays & Von Willebrand assay: For patients with + ve family h/o.

Laboratory findings Laboratory Studies Likely Diagnosis Other useful tests

Platelets PT APTT

SICK INFANTS DIC Fibrinogen, FDP, Sepsis

screen

N N

Platelet consumption(NEC, Renal vein thrombosis, marrow infiltration, Sepsis)

LFT, Albumin

N Liver disease

N N NCompromised vascular integrity(hypoxia, prematurity, acidosis)

Laboratory Studies Likely Diagnosis Other useful tests

Platelets PT APTT

HEALTHY INFANTS

N NImmune thrombocytopeniaBone marrow hypoplasia

Maternal platelet count,Platelet antigen typing, Bone marrow, Fibrinogen, FDP, Factor VII & IX assays

N Vitamin K Deficiency

N N Heriditory C.F. deficiencies

N N NBleeding d/t local factors, Plt function anomalies,Factor XIII deficiency(rare)

Platelet aggregometryUrea clot solubility

Treatment Of Bleeding

A. Inj Vitamin K1 (Aquaminophyton)- 1 mg IV or IM if not given at birth.- Infants on TPN- Infants on Antibiotics > 2 weeks: at

least 0.5mg Vit K weekly.- Preferred rather than FFP for prolonged

PT & PTT, FFP should be reserved for emergencies.

B. FFP:- 10ml/kg IV for active bleeding - Repeated 8-12 hrly as needed.- Replaces C.F. immediately.C. Platelets:- 1 Unit of platelet raises count by 50,000-

100,000/mm3 in a 3kg newborn.- Platelet count slowly decreases if stores

3-5 days.

D. Fresh whole blood:- 10ml/kg- Can be repeated after 6-8 hrs as needed.E. Clotting factor concetrates- Severe VWD : - VWF containing plasma derived factor VIII

concetrate.- Known deficiency of factor VIII or IX :

Recombinent DNA derived factor VIII and IX concetrate

F. Disorders due to problems other than hemostatic proteins :

- Rule out the underlying possibilities- eg. Infection, Liver rupture, catheter, NEC.

G. T/t of specific disorders :1. DIC :- Treat the underlying cause i.e. sepsis, NEC- Make sure that Vit K1 has been given.

- Platelets/ FFP to keep platelet counts > 50,000/ml and to stop bleeding.

- If bleeding persists, i. Exchange transfusion with fresh whole blood

/Packed RBC/Platelets/FFP ii. Continuous transfusion with platelets, packed

RBCs or FFP as needed. iii. For hypofibrinogenemia : Cryoprecipitate

(10ml/kg)

VKDB

• Early , Classic, and Late forms• Early VKDB – in first day• Severe bleeding – GI and ICH• Cause – Maternal drug intake Phenytoin, phenobarb,

ATT, warfarin

VKDBClassical form: 2-7 days of age• 0.25-1.7% of all babies• Cause – not received prophylaxis on breast feeds, sterile gut, lack

of placental transferLate form : 2-8 weeks of age• Boys > girls, 5-10/1 lac• Well , breastfed, term baby • Liver disease• Malabsorption

Management of VKDB

• Prolonged PT , APTT (if severe)• Normal platelets and fibrinogen

• Factor assays of vit K dependent factors

• Treatment – 1mg iv or sc• FFP in severe cases

Prophylaxis of VKDB

• Early VKDB- single IM inj of vit K at birth and oral Vit K to mother for last 4 weeks

• Classical and Late forms – IM Vit K at birth oral Vit K at 0 , 4 days and 4

weeks In preterms – Weekly iv Vit K

Hemophilia in the Newborn

• Factor VIII or XI deficiency– A good family history goes a long

way

Hemophilia A

• Most common inherited clotting factor def

• X linked recessive, 1 in 4000 males• 1/3rd of cases present in newborn

period• ICH(25%), cephalhematoma(10-15%) • Post circumcision bleed is

characteristic• Family history – absent in 30%• Inv – prolonged APTT, normal PT,

normal platelets.• Factor VIIIc assay level <2% severe, 2-

10% moderate, >10% mild

Hemophilia B

• XLR• Deficiency of Factor IX• Less common than the classical form• Prolonged APTT and low Factor IX• Rx- 100u/k iv OD , to raise levels to

100%• Avoid lumbar punctures, IM injections

Thrombocytopenia

• Less than 150,000/uL • Incidence in newborns: 1-5%• Incidence in NICU – 15-30%• In VLBW and preterms – 50%• Causes of thrombocytopenia in

newborn: Neonatal megakaryocytes are smaller

Inadequate production of thrombopoietin

Causes of thrombocytopenia

• Immune-mediated• Associated with infection - Bacterial or

Non-bacterial• Drug-Related • Increased peripheral consumption of

platelets – Disseminated Intravascular Coagulation, Necrotizing enterocolitis, hypersplenism

• Genetic and Congenital Anomalies• Miscellaneous – asphyxia, IUGR, PIH, GDM

Early thrombocytopenia

• Placental insufficiency (PIH, IUGR,DM)

• NAITP• Birth asphyxia• Perinatal infection• Maternal autoimmune causes( ITP,

SLE)• Congenital infection• Inherited – TAR, Wiskott- Aldrich

Late Thrombocytopenia

• Late onset sepsis and NEC• Congenital infection • Maternal ITP, SLE• Congenital / Inherited conditions

Immune Thrombocytopenia

• Neonatal allo-immune thrombocytopenia (NAIT)

• Incidental thrombocytopenia of pregnancy or Gestational thrombocytopenia

• Autoimmune thrombocytopenic purpura

Neonatal allo-immune thrombocytopenia (NAIT )

• Incompatibility between mother and baby• Similar to Rh disease• Antibodies against HPA – 1 (most common)• In utero bleed can occur• Manifests with first pregnancy in 50%• Postnatal : petechiae, purpura ICH in 10% with sequelae

NAIT

• Management – fetal blood sampling and platelet transfusion or maternal IVIG

• If previous sibling had a significant bleed

• Caesarian section• In newborn – maternal platelets or

HPA compatible platelets• IVIG 1gm/k for 2 days or 0.5g/k for 4

days

Congenital causes

• TAR , Fanconis anemia, • Congenital amegakaryocytic anemia• Trisomy 21, 18,13• Wiskott Aldrich syndrome• Noonan’s and Apert’s Syndromes

TAR (Thrombocytopenia & Absent Radii)

• Congenital• Findings

– Thrombocytopenia– Absent radii bilaterally– Small shoulders– Abnormal knees– Malabsorption

• History– Platelets stabilize– ? Leukemia

PT and APTT

• PT: measures extrinsic pathway• VII, X, II, V• Normal range : preterm:(14-22S) term : (13-20s)• APTT: Measures intrinsic pathway• VIII, IX,XI,XII, X,II, V• Uses a contact activator like kaolin , silica• Normal values: Term-(30s-45s) Preterm – ( 35 – 55s)

Thank You…