Bleeding Disorder

Sony Wicaksono
Susanto Nugroho
Lab/SMF Ilmu Kesehatan Anak
FK Universitas Brawijaya/RS Dr. Saiful Anwar

Hemostasis

Hemostasis

Vitamin K Deficiency
Bleeding

Vitamin K
A fat-soluble vitamin that can be absorbed from the
GI tract in the presence of bile salts.
Is required for the production of coagulation factor (FII,
FVII, FIX and FX) in the liver.
Inadequate intake of vitamin K can result in
deficiency in a short period of time because of:
- the short half-life of these factors, and
- the small amounts of vitamin K that can be
stored in the body.

Several Forms of Vitamin K

Vitamin K1 (Phylloquinone): green leafy vegetables

Vitamin K2 (Menaquinone): intestinal bacteria

Vitamin K3 (Menadione): synthetic form

Functions of Vitamin K
Coenzyme for the synthesis of prothrombin & blood clotting
factors in the liver
Prothrombin and clotting factors are protein in nature
Synthesis of prothrombin, clotting factors VII, IX, X
require carboxylation of their glutamic acid (Glu)
residue
Mature prothrombin and clotting factors contain gcarboxyglutamate (Gla) after carboxylation reaction
Vitamin K is essential for the carboxylase enzyme
involved
Dihydroquinone form of vitamin K is essential for this
reaction

Vitamin K Cycle

Vitamin K Cycle

Vitamin K -glutamyl
carboxylase (GGCX)

Vitamin K Cycle

Vitamin K -glutamyl
carboxylase (GGCX)

Vitamin K dependent
proteins

Vitamin K Dependent Proteins

Coagulation factors:
- Factor II (prothrombin)
- Factor VII (proconvertin)
- Factor IX (thromboplastin component)
- Factor X (Stuart factor)
Protein C & protein S
Protein Z

Functions of Vitamin K
Prothrombin platelet interaction
Carboxylated prothrombin contains two carboxylate
groups bind to Ca2+ forming prothrombin-Ca complex
The complex then binds to phosholipids on the surface
of platelets (important for blood clotting)
Converting prothrombin to thrombin & initiating clot
formation

Vitamin K Deficiency Bleeding

Why are newborns vulnerable to deficient in vitamin K ?
Placenta transfer of vitamin K is very limited
Vitamin K1 (Phylloquinone) levels in umbilical cord
blood is very low
The storage of vitamin K in neonate liver is also
limited
Breast milk is poor source of vitamin K
GI tract is sterile at birth gut-related microbial
source of vitamin K is low

Vitamin K Deficiency
Bleeding
Hemorrhagic

disease of newborn (HDN) = vitamin K

deficiency bleeding (VKDB)
VKDB is bleeding due to inadequate activities of VK-dependent
coagulation factors (II, VII, IX, X), correctable by VK
replacement.
The frequency of VKDB varies with the use of vitamin K
prophylaxis, the efficacy of prophylaxis programs, frequency
of breastfeeding, and the vitamin K content of locally
available formulas
Late VKDB has fallen from 4.4-7.2/100,000 births to 1.46.4/100,000 births in reports from Asia and Europe after
regimens for prophylaxis were instituted
Intracranial hemorrhage (ICH) is uncommon in classic VKDB
but can be observed in more than 50% of infants with lateonset VKDB

Vitamin K Deficiency Bleeding

Synonym: Vitamin K Deficiency Bleeding (VKDB),
Hemorrhagic Disease of the Newborn (HDN)
Risk factors for VKDB:
Prolonged antibiotic therapy & gastrointestinal
infections with diarrhea destroy the bacterial flora
leading to vitamin K deficiency
Most common in newborn infants

VKDB: Pathophysiology
Vitamin

K is a fat-soluble vitamin
that can be absorbed from the GI
tract in the presence of bile salts
is required for the production of
coagulation factors II, VII, IX, and X
in the liver

Short

half-life of these factors, and

the small amounts of vitamin K that
can be stored in the body,

Pathophysiology

Pathogenesis of VKDB

Vitamin K -glutamyl
carboxylase (GGCX)

Vitamin K dependent
proteins

Pathogenesis of VKDB

Hoffbrand AV, et al. 2001; Cantor AB. 2009.

Why does it happen?

Maternal

factor:

Inadequate intake
Not nursing long enough or frequently

enough
Medications taken during pregnancy
Maternal diabetes, toxemia, or placental
problems.
Undue stress during the pregnancy.

Why does it happen?

Newborn

factor

Poor feeding, or not nursing enough.

Gastro-intestinal disease or homeostasis (blockage

of bile drainage ducts in the liver, caused by

hepatitis, undeveloped bile ducts or other congenital
defects, or infection)
Medications that the mother has taken
A particularly difficult birth, resulting in birth trauma.
Prematurity
Hypoxia (lack of oxygen)
Diarrhea

Classification of VKDB
Classification by causes
1. Idiopathic
2. Secondary
- poor intake of milk
- malabsorption of vitamin K
- antagonism of vitamin K by drugs
- hepatobiliary disease (predominantly cholestasis)
Classification by age at onset
1. Early VKDB
2. Classical VKDB
3. Late VKDB

mmediate investigation/treatment of warning bleeds, help prevent the worst consequences of VKDB;
oo often is VKDB the presenting feature of a serious underlying disease which could have been
ecognized earlier.

Classification

Table 1. Forms of VKDB in Infancy

DIAGNOSIS
Clinical Features

VKDB: Clinical Features

VKDB

includes bleeding at any site

and whether spontaneous or
iatrogenic
The common sites for spontaneous
bleeding are the umbilicus, mucous
membranes, skin, gastrointestinal
and urinary tract, and
retroperitoneum
Intracranial bleeding can occur

Laboratory findings
Prothrombin

time (PT), activated partial

thromboplastin time (aPTT), fibrinogen
levels, and a platelet count in the initial
workup for bleeding in a newborn

prolonged PT usually is the first laboratory

test result to be abnormal in VKDB

NO

laboratory test can confirm the

diagnosis of VKDB.

VKDB: treatment
Vitamin

K is the mainstay of
treatment for VKDB
Severe bleeding may warrant the
use of fresh frozen plasma
Surgery when needed

Prevention
Vitamin K after
birth
Diet and
supplementation
Breast feeding

Risks of Giving the Prophylactic

Vitamin K Shot to the Baby
Too

much Vitamin K may be harmful

to baby. Levels remain 1,000 times
higher in the blood for 3-4 days after
the shot
Jaundice
Bleeding may still occur
Anaphylactic shock
Trauma at injection site (pain,
swelling)

Conclusion
3

major factors affecting coagulation

Inherited and acquired

Thank you