This document discusses various causes of hemorrhagic disease in newborns, including inherited disorders like hemophilia and von Willebrand disease, as well as acquired conditions like vitamin K deficiency, liver disease, DIC, and thrombocytopenia. It provides details on the presentation, diagnosis, and management of each condition. Key points include how hemophilia is inherited, signs of vitamin K deficiency bleeding, causes of neonatal thrombocytopenia, and treatment involving replacement of clotting factors or platelets depending on the underlying condition.

1. College Of Medicine And Health Science
School Of Graduate Studies
presentation by
Nesteho Kedir MSC maternity

2. Hemorrhagic disease of
newborn

3. content
• Introduction
• Hemophilia
• Von- Willebrand disease
• Liver disease
• Vit k deficiency
• DIC
• thrombocytopenia

4. Introduction
 Hemorrhagic disease is a bleeding problem that occurs
in a baby during the first few days of life.
 The normal range for the new-born prothrombin
(PT)and partial thromboplastin time (PTT) extend
above than those for a healthy adult.
 But there is NO increased risk of bleeding in a
healthy newborn.

5. Neonatal haemostatic system
• At birth, concentrations of the vitamin K dependent
(FII,FVII, FIX, FX) and factors (FXI, FXII) are reduced to
about 50% of normal adult values and are further
reduced in preterm infants (Hemorrhagic Disease of
Newborn).

6. Cont…
 Concentrations of the naturally occurring
anticoagulants, antithrombin, protein C, S and Z are
low at birth and as a consequence, both thrombin
generation and thrombin inhibition are reduced in
the newborn period.
• Plasminogen is also low in neonatal period
resulting in a relatively hypofibrinolytic state.

7. Causes of hemorrhage disease in newborn
• Coagulation defects
• Platelet Quantitative/ Qualitative defects
• Fibrinolytic dysfunction
• Vascular causes
• Miscellaneous

8. COMMON hemorrhagic disease of the
newborn
inherited • Haemophilia A and B
• Von- willebrand disease
• Afibrinogenesis
• Liver disease
• Vit k deficiency
• DIC
• thrombocytopnia
acquired

9. Hemophilia
• Hemophilia is an inherited bleeding disorder.
• Newborn with hemophilia can’t stop bleeding b/c
they don’t have enough clotting factor in blood.
 There are many blood clotting factors involved in
forming of clots to stop bleeding.
 Two common factors that affect blood clotting are
 factor VIII and factor IX.

10. The 3 main forms of hemophilia are:
• Hemophilia A. caused by a lack of the blood clotting
factor VIII. referred as to classic hemophilia /factor
VIII deficiency.
• Hemophilia B. caused by a deficiency of factor IX.
Referred as Christmas disease or factor IX deficiency.
• Hemophilia C. caused by lack of factor XI referred to
factor XI deficiency .

11. causes hemophilia in newborn
Hemophilia types A and B are inherited diseases. They
are passed from parents to children through a gene
on the X chromosome.
• Females have two X chromosomes, while males have
one X and one Y chromosome.
• A female carrier has the hemophilia gene on one of
her X chromosomes.

12. Cont…
• When a hemophilia carrier female is pregnant.
there is a 50/50 chance that hemophilia gene will be
passed on to the baby.
• If the gene is passed on to a son, he will have the
disease but If the gene is passed on to a daughter, she
will be a carrier.

13. The sign and symptoms of hemophilia
 Bleeding into the joints.
 Bleeding into the skin (which is bruising)
 muscle and soft tissue (called a hematoma).
 Bleeding of the mouth , nose and gums,
 bleeding that is hard to stop after losing a tooth.
 Blood found in the urine or stool
Hemophilia C usually doesn’t cause problems ,but
may have increased bleeding after surgery.

14. Diagnosis of hemophilia
 The diagnosis of hemophilia is based on patient`s
family history and a physical exam.
Blood tests include
 Complete blood count (CBC). It includes RBC, WBC
platlate, hemoglobin and hematocrit
• Clotting factors. levels of each clotting factor.
• Bleeding times. To test the speed that blood clots.
• Genetic or DNA testing. for abnormal genes

15. Hemophilia management
Treatment for hemophilia is aimed to preventing
bleeding complication (mainly head and joint bleeds).
 Bleeding in the joint may need surgery or
immobilization. The rehab of the affected joint
include physical therapy and exercise to strengthen
the muscles of affected area.
• Blood transfusions may be needed if major blood
loss has occurred.

16. Cont…
 Self-infused factor VIII or IX can allow a newborn
with hemophilia to lead a near normal lifestyle.
Factor VIII concentrates:
• Hemofil M(Baxter)
• Immunate(Baxter)
• Koate-DVI(Bayer)
Factor IX concentrates:
• Immunine(Baxter)
• Aimafix(Kedrion

17. Complications of hemophilia
• hemarthrosis
• inflammation and Long-term joint problems
• Very serious tumor-enlargements, muscle /bone
• Development of antibodies against clotting factors
• Infections from transfusions
• Hematoma
• Spontaneous nosebleed

18. Von Willebrand disease (VWD)
VWD is a genetic disorder caused by missing or
defective Von Willebrand factor (VWF), a clotting
protein. VWF binds factor VIII, a key clotting protein,
and platelets in blood vessel walls, which help form a
platelet plug during the clotting process.
• VWD is most common inherited bleeding disorder
• It is carried on chromosome 12 and occurs equally
in men and women

20. Sign and symptom of VWD
• bleeding from the gums.
• easy bruising.
• prolonged bleeding after cuts or bloodworm.
• frequent and prolonged nosebleeds.
• blood in the stool or urine.
Babies with VWD rarely bleed at birth. Babies with
Type 3 VWD, surgery, including circumcision
• soft tissue/joint bleeding (in more severe forms).

22. Diagnosis of VWD
76% of men with VWD had been diagnosed by age 10,
but 50% of women with VWD were not diagnosed
until after age 12.
• the plasma VWF protein level
•Some subtypes of type II disease are associated
with thrombocytopenia, which may be apparent
during the neonatal period and may result in
bleeding.

24. Liver Disease
• Biliary obstruction impaired vit K absorption
decrease synthesis FII,FVII,FIX and X.
• Severe hepatocellular dz, reduced FV, fibrinogen
& plasminogen activator.
• Dysfunctional fibrinogen (dysfibrinogenaemia)
• Low thrombopoietin production l/t
thrombocytopenia
• Hypersplenism associated with portal HTN l/t
thrombocytopenia

25. Vitamin K Deficiency Bleeding or VKDB
 refers to bleeding that occurs as a consequence of
vitamin K deficiency during the first six months of life.
Vitamin K refers to a group of fat-soluble vitamins
that play a role in blood clotting,
bone metabolism, and
regulating blood calcium level

26. Cont…
Coagulation factors II, VII, IX, X and other Gla-proteins
( protein C, protein S, protein Z) also depend on the
presence of vitamin K for their activity.
 vitamin K–dependent factors is characterized by
bleeding that tends to be gastrointestinal, nasal,
subgaleal, intracranial, or post-circumcision.
▪

27. Classification
Early-VKDB
▪ Onset: 0-24 hr
▪ Incidence: Rare
▪ Site: Cephalohematoma, Subgaleal, Intracranial,
Gastrointestinal, Umbilicus, Intra-abdominal.
▪ Etiology: Maternal drugs (Phenobarbital, phenytoin,
warfarin, rifampin, isoniazid) that interfere with vit K.
▪ Risk factor: Inherited coagulopathy.

28. CONT…
Classical-VKDB
▪ Onset: 2-7 days
▪ Incidence: ≈2% if infant not given vitamin K.
▪ Site: Gastrointestinal, Ear-nose-throat-mucosal,
Intracranial, Circumcision, Coetaneous, Injection sites.
▪ Etiology: Vitamin K deficiency, Breast-feeding.

29. Conti..
Late-VKDB Onset:1-6 month
▪ Incidence: Dependent on primary disease.
▪ Site: Intracranial, Gastrointestinal, Coetaneous, Ear-
nose-throat mucosal, Injection sites and Thoracic.
▪ Etiology : Cholestasis—malabsorption of vitamin K
(Biliary atresia, cystic fibrosis, hepatitis)
▪ Risk factor : Abetalipoprotein deficiency, Idiopathic
in Asian breastfed infants, Warfarin ingestion.

30. causes vitamin K deficiency
– Minimal transplacental passage of vitamin K
– Limited hepatic storage of vitamin k in newborn
– Low concentration of vitamin k in breast milk
– Absence of the bacterial intestinal flora normally
responsible for the synthesis of vitamin K
not receive a vitamin K shot at birth.

31. presentations of VKDB
 Bruises on the baby's head;
 External bleeding, especially from the nose or
umbilical cord;
 Unnatural skin coloring.
 Vomiting blood.
 Stool that is dark and sticky.
 irritability, convulsions, poor reflexes and poor
feeding.

32. Investigation
▪ Coagulation profile : Prothrombin time (PT),
activated partial thromboplastin time (aPTT),
fibrinogen levels, and a platelet count should be
included in the initial workup for VKDB in a newborn.
– A prolonged PT is usually the first laboratory test
result will be abnormal in VKDB
– Normal aPTT, fibrinogen levels and a platelet count .
– Factor assay.

33. CONTI..
 Imaging study : CT scan ,MRI,USG
▪ CBC
▪ LFT
▪ Stool for occult blood
▪ ERCP
▪ Liver biopsy

34. Differential DX of VKDB
▪ Alloimmune Thrombocytopenia
▪ Consumption Coagulopathy
▪ Hepatobiliary Disease
▪ Maternal Isoimmune Thrombocytopenia
▪ Pediatric Von Willebrand Disease
▪ Uncommon Coagulopathies
▪ Swallowed blood syndrome

35. Types of vitamin k
K1: Phylloquinone is predominantly found in green
leafy vegetables, vegetable oils, and dairy products. ...
K2: Menaquinone is synthesized by gut flora.
K3: Menadione is a synthetic, water soluble form that
is no longer used medically because of its ability to
produce hemolytic anemia.

36. Management
The disease may be effectively treated with a slow IV
infusion of 1-5 mg of vitamin K1.
▪ Serious bleeding, particularly in premature infants or
those with liver disease, may require a transfusion of
fresh frozen plasma or whole blood.

37. CONT…
Surgical Care
▪ Normally, VKDB infants do not require surgical care
but in rare cases, an infant may need neurosurgical
evaluation and treatment.
▪ Other conditions, such as those associated with
short bowel syndrome and Hepatobiliary disease may
require surgical evaluation

38. Complication
▪ Intracranial hemorrhage is the primary serious
complication of VKDB
▪ Complications of treatment include anaphylactoid
like reactions during intravenous (IV) vit K admin,
hyperbilirubinemia or hemolytic anemia after high
doses of vitamin K, and hematomas at the site of
injection.

39. Prevention
▪ Early-VKDB : Administrations of vitamin K to infant
at birth or to mother (20 mg) before birth.
▪ Classical-VKDB: Parenteral vitamin K at birth.
▪ Late-VKDB: Parenteral and high-dose oral vitamin K
during periods of malabsorption or cholestasis.

40. Disseminated intravascular coagulation
DIC is an acquired syndrome characterized by
excessive systemic activation of coagulation, resulting
in both hemorrhage and thrombosis. DIC can progress
rapidly into life-threatening multiorgan failure
DIC always occurs as a secondary event, and a
number of prenatal and neonatal problems are
associated with.

41. Etiology
birth asphyxia, acidosis, respiratory distress
syndrome, infection, necrotising enterocolitis,
meconium aspiration, aspiration of amniotic fluid,
brain injury, hypothermia, giant haemangioma,
homozygous protein C/S deficiency, thrombosis,
malignancy.

42. The laboratory diagnosis of DIC
typical pattern of reduced platelets,
PT, APTT with or without thrombin clotting time),
reduced fibrinogen, and increased D-dimers
Although this pattern is likely to be present in a
neonate with fulminating DIC, findings can vary, and a
number of factors complicate the diagnosis during the
neonatal period.

43. manifestations of DIC in neonate
Bleeding , bruising , low blood pressure, shortness
of breath, confusion.
Managemanet
Treatment by underlyding cause
Fresh frozen plasma (10–15 ml/kg) can be used to
replace haemostatic proteins,
cryoprecipitate (5–10 ml/kg) is a better source of
fibrinogen, which should be kept above 1 g/l

44. Neonatal thrombocytopenia
Thrombocytopenia in neonates is traditionally defined
as a platelet count <150000/mcL
 over all incidence of neonatal
thrombocytopenia is (0.7%–0.9%)
 In Neonatal Intensive Care Unit (NICU) it is
very high (22%–35%)

45. classifications
Mild- (PC = 100000 – 150000/mcl)
Moderate (PC = 50000 – 99000/mcl)
Severe (PC < 50000/mcl)

46. CONDITION
Fetal Alloimmune condition
Congenital infection (e.g., CMV,
toxoplasma, rubella, HIV)
Aneuploidy (e.g., trisomy 18,13, or 21, or
triploidy)
Autoimmune condition (e.g., ITP,
SLE)
Severe Rh hemolytic disease
Congenital/inherited (e.g.,Wiskott-
Aldrich syndrome)

47. CONDITION
Early-onset
neonatal (<72
hr)
Placental insufficiency (e.g., IUGR, diabetes)
Perinatal asphyxia
Perinatal infection (e.g., Escherichia coli, GBS, Haemophilus
influenzae), DIC
Alloimmune condition
Autoimmune condition (e.g., ITP, SLE)
Congenital infection (e.g., CMV, toxoplasma, rubella, HIV)
Thrombosis (e.g., aortic, renal vein)
Bone marrow replacement (e.g., congenital leukemia)
Kasabach-Merritt syndrome
Metabolic disease (e.g., proprionic and methylmalonic acidemia)
Congenital/inherited (e.g., TAR, CAMT)
CONDITION
Early-onset
neonatal (<72
hr)
Placental insufficiency (e.g., IUGR, diabetes)
Perinatal asphyxia
Perinatal infection (e.g., Escherichia coli, GBS, Haemophilus
influenzae), DIC
Alloimmune condition
Autoimmune condition (e.g., ITP, SLE)
Congenital infection (e.g., CMV, toxoplasma, rubella, HIV)
Thrombosis (e.g., aortic, renal vein)
Bone marrow replacement (e.g., congenital leukemia)
Kasabach-Merritt syndrome
Metabolic disease (e.g., proprionic and methylmalonic acidemia)
Congenital/inherited (e.g., TAR, CAMT)

48. Immune thrombocytopenia
Immune thrombocytopenia occurs due to passive
transfer of antibodies from the maternal to the fetal
circulation.
Types:
1) Neonatal Alloimmune thrombocytopenia (NAIT)
2) Autoimmune thrombocytopenia

49. Neonatal Alloimmune thrombocytopenia (NAIT)
 antibody is produced in the mother against specific
human platelet antigen (HPA) present in the fetus but
absent in the mother.
 The antigen is inherited from the father of the fetus.
 Early onset severe thrombocytopenia.
 combination of severe neonatal thrombocytopenia
with a parenchymal (rather than intraventricular)
intracranial hemorrhage is highly suggestive of NAIT.

50. Diagnosis and management of NAIT
Investigation :
1) Antigen screening (HPA 1,3,5,9,15,4)
2) Brain imaging studies
Management:
1) Suspected NAIT in an unknown pregnancy
2) Known case of NAIT
3)Antenatal mgt of pregnant woman with previous
history of NAIT

51.  Management of the neonate with suspected NAIT in an
unknown pregnancy.
1) Random-donor platelet transfusion
2)IVIG (1g/kg/day for 2 days)
3) Antigen-negative platelet transfusion
4) Methylprednisolone (1 mg/kg bid for 3–5 days)
 Management of the neonate with known NAIT
Antigen-negative platelet transfusion
 Antenatal management of pregnant women with previous
history of NAIT IVIG is given to mother.

52. Guidelines
for platelet
transfusion

53. Platelet Count (*10000mcl)
<30 Transfuse all
30-49 Transfuse if:
• BW <1,500g and & 7 days old
• Clinically unstable
• Concurrent coagulopathy
• Previous significant hemorrhage
(i.e., grade 3 or 4 IVH)
• Prior to surgical procedure
• Postoperative period (72 hours)
50–100 Transfuse if:
• Active bleeding
• NAIT with intracranial bleed
•Before or after neurosurgical
procedures
 Dose: 10 -15 ml/kg

54. Complications:
Transfusion-transmitted CMV infections
Graft-versus-host disease (GVHD)
TRALI

55. Clinical
Evaluation Platelets PT PTT Likely diagnosis
Sick D- 1+ 1+ DIC
D- N N
Platelet consumption ( infection,
necrotizing enterocolitis, renal vein
thrombosis )
N 1+ 1+ Liver disease
N N N
Vasculitis (hypoxia, prematurity,
acidosis, hyperosmolality )
Healthy D- N N
ITP, occult infection, thrombosis, B.M.
hypoplasia or infilteration
N 1+ 1+
Hemorrhagic disease of newborn ( vit.
K deficiency )
N N 1+ Hereditary clotting factor deficiencies
N N N
Bleeding due to local factor ( trauma,
anatomic anomalies);
PT = prothrombin time; PTT = partial thromboplastin time; D- = decreased; 1+ = increased; DIC =
disseminated intravascular coagulation; N= normal .

56. References
▪ Nelson Textbook of Pediatrics
▪ Manual of Neonatal Care-Cloherty
▪ oxford handbook of neonatology
▪ Medscape
 Clinicalkey

57. THANK YOU