ACQUIRED COAGULATION DISORDER
A. DEFICIENCIES OF VITAMIN KDEPENDENT FACTORSProthrombin;
factors VII, IX, and X; and proteins C and S are synthesized by the
liver by a process that depends on vitamin K. When stores of this
vitamin are deficient or abnormal, hypofunctional analogs of these
factors are synthesized, which inhibit normal coagulation. These
descarboxy analogs of the vitamin Kdependent factors do not bind to
cellular phospholipid surfaces and, therefore, do not participate
in cell-associated coagulation reactions. This may occur in
disorders in which intake or absorption of vitamin K is deficient
and in disorders that impair the biosynthetic capacity of the
liver. A similar coagulation abnormality may be produced by
anticoagulant drugs such as coumarin and indanediones, which
antagonize the action of vitamin K.PATHOPHYSIOLOGY The normal
newborn has a moderate but significant deficiency of the vitamin
Kdependent coagulation factors. The plasma levels of these factors
normally fall even further during the first 2 to 5 days of life,
rise again when the infant is 7 to 14 days old, and attain normal
adult levels at approximately 3 months of age. This sequence of
events normally does not produce bleeding. However, in VKDB, the
initial fall is accentuated, and the secondary restoration is
delayed and incomplete. As a consequence, coagulation abnormalities
become severe, and bleeding results. The deficiency of the vitamin
Kdependent coagulation factors that is present at birth, as well as
the slow rate at which adult levels are attained, presumably is the
result of intrinsic liver immaturity; neither of these physiologic
phenomena is affected by vitamin K administration. On the other
hand, the diminution in levels of these factors that occurs at age
2 to 5 days is prevented by vitamin K administration because it is
the result of a transitory physiologic deficiency of this vitamin.
Factors that further diminish the amount of vitamin K available at
this juncture and those that further impair the synthetic capacity
of the liver predispose neonates to hemorrhagic disease of the
newborn. These factors are (a) prematurity(b) inadequate dietary
intake(c) delayed gut colonization by bacteria(d) various obstetric
and perinatal complications, and, possibly(e) maternal deficiency
of vitamin K. Prematurity often has been associated with VKDB.
Levels of the vitamin Kdependent factors at birth are approximately
proportional to gestational age and birth weight. In premature
infants, the physiologic immaturity of the liver is marked, and the
response to vitamin K that is present is subnormal. Most factors
associated with deficient intake of vitamin K also delay the
colonization of the gut by bacteria. These factors include delayed
feeding, breast-feeding, vomiting, severe diarrhea, and
antibiotics, including those present in maternal milk. Human milk
and colostrum are poor sources of vitamin, and reliance on breast
milk as the sole source of nutrients in the neonatal period is an
important factor in many cases of VKDB. Coumarin and indanedione
drugs cross the placenta and may produce hemorrhagic disease in the
newborn. Infants born of mothers who were taking diphenylhydantoin
or other anticonvulsants, including barbiturates, or salicylates
have developed a syndrome similar to VKDB. Treatment of the mother
with vitamin K during the last trimester may prevent this
complication. CLINICAL FEATURES AND LABORATORY DIAGNOSIS VKDB
etiology is considered idiopathic (no cause other than
breast-feeding) or secondary (malabsorption of vitamin K, liver
disease, drugs). VKDB can also be classified in terms of age of
onset: early (onset
