ACQUIRED PROTHROMBIN COMPLEX DEFICIENCYAcquired prothrombin complex deficiency:

A rare disorder where infants with a deficiency of vitamin K sufferproblems with bleeding. It is believed to
occur in breast fed infants where the milk from the mother lacks sufficient vitamin K. low.
Causes
Vitamin K deficiency is common among neonates in the first few days postpartum due to poor
placental transferof vitamin K and inadequate production of vitamin K-producing intestinal flora. Its
other causes includeprolonged use of drugs, such as the anticoagulant warfarin and antibiotics that
destroy normal intestinalbacteria; decreased flow of bile to the small intestine from obstruction of
the bile duct or bile fistula;malabsorption of vitamin K due to sprue, pellagra, bowel resection,
ileitis, or ulcerative colitis; chronic hepaticdisease, with impaired response of hepatic ribosomes to
vitamin K; and cystic fibrosis, with fat malabsorption.Vitamin K deficiency seldom results from
insufficient dietary intake of this vitamin.
Signs and symptoms
The cardinal sign of vitamin K deficiency is an abnormal bleeding tendency, accompanied by
prolongedprothrombin time (PT); these signs disappear with vitamin K administration. Without
treatment, bleeding may besevere and, possibly, fatal.
Diagnosis
Confirming diagnosis
A PT thats 25% longer than the normal range of 10 to 20 seconds, measured by the Quick method, confirms
the diagnosis of vitamin K deficiency after other causes of prolonged PT (such as
anticoagulant therapy or hepatic disease) have been ruled out. The International Normalized Ratio
(normal value, 0.8 to 1.2) isthe more common method of assessing PT adequacy.
Repetition of testing in 24 hours (and regularly during treatment) monitors the therapys
effectiveness.

Treatment
Administration of vitamin K I.V. or I.M. corrects abnormal bleeding tendencies.
Deficiency Symptoms of Vitamin K

Deficiency Symptoms In Newborns

Vitamin K deficit in newly born babies can cause haemorrhagic disease that has the potential to cause grave complications. Infants
with classic vitamin K deficit are oftentimes sick, have postponed feeding or exhibit both these together. Over half of such babies

have acute intra-cranial hemorrahage. Blood loss generally is noticed in the gastrointestinal tract, nose, omphalos, operated sites
(for e.g. site where the infant was circumcised) and rarely the brai

Vitamin K Deficiency

According to Mayo Clinic, insufficiency of vitamin K atypically occurs since majority of the individuals are getting ample amounts
from dietetic intake and bacterial forms in intestines. But, adults can suffer from vitamin K deficit due to factors like improper diet,
extensive usage of antibiotic medicines like cephalosporin, neomycin and tetracycline that obliterate dire and favourable bacteria
in the intestines. Also, the use of statins or other lipid-lowering medications might lead to vitamin K deficit by hindering the uptake
of lipo-soluble vitamins.

Background
Prothrombin (factor II of the coagulation cascade) is a critical protein in hemostasis. Decreased levels of prothrombin can lead to a
bleeding diathesis. The most common manifestations of hypoprothrombinemia are associated with mucocutaneous bleeding. However,
hemorrhage involving deep structures can be observed with severe prothrombin deficiency.
Hypoprothrombinemia may be acquired or inherited. Acquired forms may be secondary to decreased production or increased
consumption. Acquired isolated hypoprothrombinemia is usually autoimmune and associated with the lupus anticoagulant. A relatively
common form of acquired hypoprothrombinemia is vitamin K deficiency. Levels of other vitamin Kdependent procoagulant factors
(factors VII, IX, and X) and anticoagulant factors (protein C and protein S) are also decreased in vitamin K deficiency.
Inherited prothrombin deficiency is rare. [1] Two phenotypes are described: hypoprothrombinemia (type I deficiency) and
dysprothrombinemia (type II deficiency). In type I deficiency, prothrombin levels and prothrombin activity are reduced. In type II
deficiency, prothrombin activity is reduced, but prothrombin levels are borderline or in the reference range. Both disorders are
autosomal recessive. The prothrombin gene is found on chromosome 11. Heterozygotes for prothrombin deficiency have factor II
levels of 30-60% of the reference range. Heterozygotes are usually asymptomatic. Compound heterozygotes who have type I and type
II mutations are occasionally reported.

The treatment of hypoprothrombinemia depends on the underlying etiology. Plasma-derived products that contain factor II are
available. Vitamin K-1 (phytonadione) is used to treat vitamin K deficiency as well as warfarin overdose. In autoimmune disease,
treatment is not entirely straightforward, and immunosuppressive therapy is used in severe cases.

Epidemiology
Frequency

United States
Both acquired and inherited hypoprothrombinemia are exceedingly rare in the United States. Hypoprothrombinemia due to vitamin K
deficiency is rarely seen because vitamin K injections are routinely given in the neonatal period.
International
The estimated prevalence of inherited prothrombin deficiency worldwide is 1 per 2,000,000 population. The prevalence is higher
where consanguinity is common. In parts of the world where vitamin K is not routinely administered in the neonatal period,
hypoprothrombinemia secondary to vitamin K deficiency is relatively common. The incidence of hemorrhagic disease of the newborn
in the absence of active prophylaxis is about 1 in 500 newborns.
Mortality/Morbidity

In both acquired and inherited hypoprothrombinemia, the morbidity and mortality risks are related to the circulating level of factor II.
The risks are less than 2% with severe deficiency, 2-10% with moderate deficiency, and 10-40% for mild deficiency.
In a prothrombin knockout-mouse model, complete prothrombin deficiency led to a 50% mortality rate on embryonic day 10.5. [2]
Some embryos survive to birth but die from hemorrhaging on the first day. In humans, severe life-threatening hemorrhage, including
intracranial hemorrhage, is described in neonates with severe prothrombin deficiency. Severe prothrombin deficiency is likely to lead
to spontaneous abortion and fetal demise in some cases. Complete prothrombin deficiency in humans has not been reported; this
omission suggests that this condition is incompatible with life.

Race

No race predilection for hypoprothrombinemia is apparent. However, in 2003, the North American Registry for Rare Bleeding
Disorders reported that 62% of patients with prothrombin deficiency in the United States and Canada were Hispanic. [3]
Sex

Acquired hypoprothrombinemia associated with the lupus anticoagulant is slightly more common in women than in men. Severe
inherited prothrombin deficiency typically has an autosomal recessive inheritance pattern. Therefore, unlike classic hemophilia, severe
inherited prothrombin deficiency occurs with equal frequency in male and female individuals.
Age

Patients with inherited severe hypoprothrombinemia present early in life, whereas patients with mild forms present at various ages. [4]
Vitamin K deficiency is most common in young infants. Patients with autoimmune hypoprothrombinemia can present at any age.