2. The hemoststic mechanism in neonate different from older
children. There is decreased activity of several clotting factors,
diminished platlet function and sub optimal defence against clot
formation On presentation Stabilize Assess vitals severity of
disorder Replace fluids adequately Monitor Evaluate for cause
4. Clotting factors defects 1)Transitory deficiencies :
Procoagulant vit k dependent factors 2 ,7,9 and 10 and
anticoagulant protein C and S and may be attenuated by
Administration of total parentral alimentation or antibiotics or
lack of administration of vit k to premature infants. Term infant
may develop vit k deficiency by day 2 or 3 if they are not
supplemented vit k. Mother might have received certain drug during
pregnancy that can cause bleeding in first 24hr of infant life like
phenytoin, phenobarb, salicylates warfarin.
5. 2)Disturbance of clotting : may be related to associated
disease such as DIC ,due to infection, shock anoxia, NEC ,renal
vein thrombosis, vascular catheter, liver disease. 3)Inherited
abnormalities of clotting factors X linked recessive (present in
male,affected is female) a)Factor 8 levels are decreased in newborn
with hemophilia A (1 in 5000). b) Heamophilia B or christmas
disease is due to deficiency of factor 9 (1 in 25000)
6. Autosomal dominant: (expressed in boys and girl with one
parent affected) Von willebrand disease is due to decreased levels
or functional activity of VW factor.It is the most common inherited
coagulation defect. Dysfibrinogenemia is due to fibrinogen
structural mutation. Autosomal recessive: (occur in both boys and
girls born to carrier parents) Deficiency of factor 11, 7 ,5,10,2,
fibrinogen and 13 are all encoded by autosomal gene.
7. COMMON COAGULATION DISORDER Haemophilia A and B Von-
willebrand disease Factor VII, X,XII deficiency afibrinogenesis
Inherited Liver disease Vit k deficiency Warfarin overdose DIC
acquired
9. DIFFERENCES IN BLEEDING PATTERN PLATELET DISORDER
COAGULATION DISORDER SITE OF BLEEDING Skin, mucous membrane Deep in
soft tissue, joints, muscles PETECHIAE yes no ECCHYMOSES Small,
superficial Large, deep HEMARHTROSIS/ MUSCLE BLEEDING Extremely
rare common BLEEDING AFTER MINOR TRAUMA yes no BLEEDING AFTER
SURGERY Immediately, mild Delayed(12 days), severe EXAMPLES vWD ITP
Hemophilia A, B
10. Vascular causes of bleeding Pulmanory and CNS hamorrage
Henoch schonlein purpura Connective tissue disease Scurvy
Hemanangioma. Hereditary hemorrhagic telangiectasia Miscellaneous
problems: Trauma: rupture of spleen or liver with breech delivary.
Subdural hematoma, subgaleal and cephalohematoma.
11. Hematologic consequences to the fetus due to maternal
disease Diabetes : polycythemia and thrombosis Hypertension :
neutropenia, thrombocytopenia SLE : thrombocytopenia or thrombosis
Smoking : polycythemia Medications : aspirin effects on hemostasis
Chemotherapy thrombocytopenia Intrauterine infection : anemia
(hemolytic), thrombocytopenia, consumptive coagulopathy.
12. Clinical approach to the bleeding neonate A detailed
history including detailed past history and family history. A
careful physical examination. Screening tests. Specific tests for
hemostasis as required, need to be done to define the defect .
13. HISTORY TAKING : Is the infant sick or well at the onset of
bleeding? Sites of bleeding. Onset, severity and duration
Spontaneous or after trauma. Symptom correlate with degree of
injury or trauma? Does bruising occur spontaneously? If there was
any chord bleeding? Has vitamin K been given to the infant? Is
there a family history of bleeding disorder? History of maternal
illness, maternal infection, drug intake
14. Presentations in newborn are unique EXCESSIVE BLEEDING can
appear as Expanded cephalhematoma. Prolonged bleeding after
circumcision. Oozing from venipuncture site and line placement
site. Bleeding from umbilicus . Sick neonate may present as Bleed
from bladder haematuria Mucous membrane bleed IC bleed Pulmonary
haemorrage
15. PHYSICAL EXAMINATION VWD, PLATELET FUNCTION DEFECTS
CLOTTING FACTOR DEFICIENCY
16. Examine for Degree of anemia Ecchymoses Petichiae Vascular
malformations Rashes splenomegaly Rule out local causes of
bleeding
17. ON EXAMINATION Sick infant DIC, infection, liver diseases
Well infant VKDB ,Clotting factor deficiency. Petechiae, small
ecchymosis platelet disorder Large bruises clotting factors
defeciency, DIC, liver disorders ,or vit k defeciency Splenomegaly
congenital Infection/erythroblastosis. Jaundice TORCH infections or
LIVER disease Abnormal retinal finding-TORCH infection
18. Bleeding Neonates: sick or well Acquired Causes Most Common
Acquired coagulopathy: More likely in sick infants Inherited
bleeding disorders or immune thrombocytopenias: more often in well
infants Alloimmune thrombocytopenia (NAIT) Review obstetric and
neonatal course DIC Acidosis, RDS, meconium aspiration,
hypothermia, NEC, sepsis, exchange transfusion, etc Review family
history of bleeding Immune thrombocytopenia (ITP) or Neonatal
19. Likely diagnosisPTTPTPlatelets Clinical Evaluation
DIC1+1+D-Sick Platelet consumption ( infection, necrotizing
enterocolitis, renal vein thrombosis ) NND- Liver disease1+1+N
Vasculitis (hypoxia, prematurity, acidosis, hyperosmolality )NNN
ITP, occult infection, thrombosis, B.M. hypoplasia or
infilterationNND-Healthy Hemorrhagic disease of newborn ( vit. K
deficiency ) 1+1+N Hereditary clotting factor deficiencies1+NN
Bleeding due to local factor ( trauma, anatomic anomalies); NNN PT
= prothrombin time; PTT = partial thromboplastin time; D- =
decreased; 1+ = increased; DIC = disseminated intravascular
coagulation; N= normal .
20. The Workup Continues False positive evaluations Need to
interpret lab results in context of developmental hemostasis
Pediatric reference ranges False negative evaluations Often miss
mild disorders in newborns (Mild hemophilia, type 1 and 2 von
Willebrand disease) Platelet function disorders not evaluated Rare
bleeding disorders
21. Swallowed blood syndrome Blood or bloody stools are passed
during the 2nd or 3rd day of life due to swallowing of maternal
blood during delivery or from a fissure in the mothers nipple . It
may be confused with hemorrhage from GIT of the newborn . The Apt
test is used to DD, based on the fact that the infants blood
containing hemoglobin mostly HbF is alkali- resistant where as the
maternal blood (Hb A) forms alkaline hematin on addition of alkali
.
22. Laboratory tests TEST FOR PLATELET DISORDER. BLEEDING TIME:
assesses the function of platelets & their interaction with
vascular wall. (Normal range:4-8 minutes) PLATELET COUNT: normal
(150,000-400,000) PLATELET FUNCTION ANALYSIS (PFA-100) PLATELET
AGGREGATION STUDY: with ADP, Epinephrine, collagen , thromboplastin
and Restocetin is done. TEST FOR COAGULATION FACTOR. aPTT: measure
the initiation of clotting at level of intrinsic factor VII,IX,XI
(normal 25-40s.) PT: measures the extrinsic clotting limb i.e.
II,V,VII,X. (12-14s) THROMBIN TIME:- measures final step of
clotting cascade. (Normal 11-15 s) prolonged in fibrinogen
deficiency. Fibrinogen. D Dimer assays. Peripheral smear platelet
and RBC morphology
23. Treatment of bleeding in neonate 1. I.V. infusion of 1-5 mg
vit. K1will lead to cessation of bleeding within a few hours. 2.
Fresh frozen plasma (10 ml/ kg) in cases of serious bleeding,
premature NB, those with liver diseases and ineffective vit. K
therapy. 3. Whole blood transfusion (in case of marked hemorrhage )
may be required 4-Treatment of the underlying cause: * Platelets :
In case of thrombocytopenia, 1 unit of platelets given to a 3-kg
infant will raise the platelet count to 50.000-100.000 / mm. *
Clotting factor concentrates : In cases of inherited deficiencies
of F8, or F9, but plasma may be sufficient . * Treatment of
disseminated intravascular coagulopathy a. Treatment of the
underlying cause ( sepsis, NEC ). b. If the bleeding persists :
Exchange transfusion with fresh whole blood . c. If thrombosis of
large vessels : Heparin : bolus of 25-35 units / kg, followed
by10-15 units / kg / hr. as a continuous infusion. Keep the PTT at
1.5-2 times normal.
24. (Hereditary Clotting Factor Deficiency) HEMOPHILIA A OR B
Most common inherited clotting disease. Hemophilia A and B are
inherited bleeding disorders caused by deficiencies of clotting
factor VIII (FVIII) and factor IX (FIX), respectively. They account
for 90-95% of severe congenital coagulation deficiencies. Affect
all racial groups. X-linked recessive disorders; therefore, they
affect males almost exclusively. Reports of affected females are
rare.
25. Hemophilias may be undiagnosed in the newborn. Its noticed
when a child begin to crawl & walk because mobility causes the
initiation of easy bruising, intramuscular hematoma &
hemoarthrosis. In the newborn factor VIII level may be artificially
elevated because of acute phase response elicited by the birth
process. In contrast, factor IX level is physiologically low in the
new born. LABORATORY FINDINGS: Reduced level of factor VIII or
factor XI. Prolonged Clotting time & aPTT. Normal Platelet
count , BT, PT & thrombin time. Prolonged thromboplastin
generation time.
26. Von Willebrand disease VWD is the commonest inherited
bleeding disorder, with an estimated prevalence of 0.81.3%
Inherited as an autosomal dominant disorder. Both superficial
bleeding problems and ICH have been reported in affected neonates.
Type IIb vWD can also be recognized at this time due to the
presence of thrombocytopenia Most other forms of vWD are masked by
physiologically elevated levels of vWF and cannot be diagnosed in
neonates other than by molecular analysis DIAGNOSIS: Type III vWD:
low levels of both FVIII and vWF. Some cases of type II vWD may
also be diagnosed in the neonate where there is reduced vWF
activity.
27. Moderate transient deficiencies of vitamin K dependent
factors 2, 7, 9,10 1. Reduced body store of vit K of the newborn
due to lack of free vitamin K in the mother (more common among the
preterm infants). 2. No vitamin K administration after birth.
(Breast milk is a poor source of vitamin K) more common in
breast-fed infants than formula-fed ones ). 3. Liver immaturity or
disease. 4. Malabsorpation disease (biliary atresia, cystic
fibrosis, hepatitis). 5. Absence of bacterial intestinal flora
(that form vitamin K): Total parenteral alimentation , Broad
spectrum antibiotics. 6. Maternal medication : phenytoin,
phenobarbital, salicylates, rifampcin and isoniazid
28. EARLY VKDB Least common form. The onset: within the rst 24
hours of life. Bleeding pattern is variable but can be serious, ICH
does occur. Typically,(not exclusively), associated with the drug
ingestion during pregnancy. Warfarin, anticonvulsants and the
antituberculous drugs rifampicin and isoniazid have all been
implicated. MANAGEMENT At risk mothers should be given about 10 to
20 mg/day of vitamin K orally for 15 to 30 days before delivery.
When Warfarin is to be prescribed it is advised that it is avoided
between wks 6 &12 of gestation(Teratogenic) and close to term
(neonatal bleeding.)
29. CLASSICAL VKDB Estimates of the frequency of classical VKDB
in the absence of vitamin K prophylaxis vary considerably (0.25
1.7%) and depend particularly on the method of feeding employed.
They are almost exclusively breast-fed. Typically presents between
days 2 and 5 in infants who appear otherwise well. Bruising,
purpura and gastrointestinal hemorrhage are typical presentation.
Bleeding from the umbilicus and mucous membranes is also common,
but ICH appears to be relatively infrequent. MANAGEMENT:- I/V or
S/C Vit K Transfusion therapy Supportive treatment
30. LATE VKDB The onset is after the rst week of life, with a
peak incidence between 2 and 8 weeks. ICH is seen in around 50% of
cases and is associated with significant morbidity and mortality.
Breast-feeding and failure to receive vitamin K at birth are
frequently documented risk factors. it can be the presenting
feature of cystic fibrosis, celiac disease, anti-antitrypsin
deficiency and biliary atresia. In other cases it is thought that
transient, mild abnormalities of liver function may contribute to
cholestasis and temporarily reduced vitamin K absorption.
31. Disseminated Intravascular Coagulation DIC is a
clinicopathologic syndrome resulting into widespread intravascular
coagulation induced by procoagulants that are introduced into or
produced in the blood circulation and overcome the natural
anticoagulant mechanisms. Spectrum of DIC includes: Thrombosis
Bleeding Progressive organ dysfunction The end result is usually
hemorrhage.
32. Management of DIC DIC is a secondary phenomenon ,management
is reversal of the underlying disease process. Supportive therapy
with FFP, cryoprecipitate and platelets to maintain adequate
hemostasis. The platelet count should be maintained above 50 109/L.
FFP (10 15 mL/kg) can be used to replace hemostaticproteins,
including the coagulation inhibitors ATIII, protein C & S.
Cryoprecipitate (5 10 Ml/kg) is a better source of brinogen, which
should be maintained above 1 g/L. Red cell concentrates are also
frequently required. Exchange transfusion may be undertaken in
sepsis induced DIC.
33. REFERENCES Fanaroff and martin neonatal perinatal medicine
9th edition 2012 ,pg no 1334-1345. Averys neonatology 6th edition,
pg no 1190-1195. Manual of neonatal care, john p cloherty 7th
edition pg no538-545 Care of newborn ,Meherban Singh 7THEdition pg
no 355-365. Google search :oskis text book of pediatrics . Case
reports from journals .
