Vitamin

Deficiency DR.MUJEEBULLAH MAHBOOB

PED-MED RESIDENT AT FMIC 19/10/2015

Contents of the presentation Overview of vitamin k

Physiological functions of vitamin k

Vitamin K deficiency

Clinical findings of VKD

Laboratory findings

Diagnosis and Dx

Treatment of VKD

Prevention of VKD

Conclusion

Overview of Vitamin k is a fat soluble vitamin necessary for the

synthesis(activation) of clotting factors :

a. Clotting factor II(prothrombin)

b. Clotting factor VII(proconvertin)

c. Clotting factor IX(thromboplastin)

d. Clotting factor X(Stuart factor)

So sometimes it is also called “clotting vitamin”

Overview of… Biochemically the term vitamin k refers to all those

compounds that have the common naphthoquinone ring structure bellow:

Overview of… Based on the alkyl-(R) group vitamin k may be

classified as: vitamin K1 (Phllyoquinone) --- R-phytyl

vitamin K2 (menaquinone)--- R-prenyl

vitamin K3 (menadione)—no side chain

Vitamin K1 (Phylloquinone) One of the natural forms of vitamin k found in plant

sources (Green leafy vegetables such as cabbage, spinach, cauliflower are highly rich in vitamin k)

Animal sources (liver) are intermediate and cereals low in having vitamin k.

Vitamin k1 is used to fortify foods and as a medication an the united states.

Vitamin K2 (menaquinone) Menaquinone is produced by intestinal bacteria and

also present in animal origin foods like:

Meat especially liver

Cheese

Menaquinone is used pharmacologically in some countries.

Synthetic forms of vitamin K Vitamin k also has two synthetic forms known as:

Menadiol or Menadione

Menadiol diacetate

These two synthetic forms are converted to menaquinone in the liver.

Both synthetic forms are water soluble and are for treatment of VKD.

Absorption and

metabolism Water soluble vitamin absorb directly into portal

blood.

Fat soluble vitamins

Absorbed from intestine via lymph (requires bile salts for absorption)

Temporarily stored in liver

Metabolized by side chain cleavage (glucuronide conjugation )

Metabolites are excreted in bile &

urine

Physiologic Functions Vitamin k is a necessary factor for blood coagulation

because it plays role is as a cofactor in the synthesis of

clotting factors II, VII, IX, X.

It is necessary for Synthesis of anti-coagulation Proteins C,S,.

Also necessary for formation of protein Z.

Mechanism of Action

Vitamin k deficiency, Etiology At Birth or first 24hours of life

1-14 days of life 2-12 weeks of life Beyond infancy

a) Maternal intake of medications like: anti-TB(rifimpine,INH), Anti-convulsants(phenobarbital, phenytoin), vitamin k antagonists(warfarin), some cephalosporin's.

a) Poor transport across the placenta

b) No intestinal synthesis of vit-k2

c) Inadequate intake

d) No post-natal prophylaxis

e) Breast-fed newborns (delayed feeding)

a) Breast-feeding b) Malabsorption

Syn (C.F, Biliary obstruction)

c) Chronic use of broad-spectrum Abx

d) Diarrhea, Hepatitis

a) Fat-malabsorption

b) Prolonged use of broad-spectrum Abx.

c) TPN without vit-k supplementation.

d) Lack of oral intake.

Vitamin k deficiency… Fat malabsorption can cause vitamin k deficiency at

any, these syndromes include:

Cholestatic liver diseases (biliary atresia, alpha-1 antitrypsin deficiency.

Pancreatic diseases

Intestinal disorders (celiac sprue, IBD, short-Bowel Syn)

C.F if liver diseases and pancreatic insufficiency was present.

Vitamin k deficiency… Prolonged diarrhea can cause vitamin k deficiency

especially in breast-fed infants.

Its enough for a patient to receive at least for 10 days a broad-spectrum anti-biotic to cause vitamin k deficiency in that patient. (kaplan Med)

Clinical Manifestations of VKD VKD causes a systemic bleeding disorder in newborn

infants, the Vitamin k-deficiency bleeding (VKDB) of the newborn.

Mild vitamin k deficiency can affect long-term bone and vascular health.

Clinical Manifestations of VKD Intracranial bleeding can cause convulsion,

permanent sequelae or death.

In some cases of VKD the presence of the underlying cause can be suggested in the form of Jaundice or Failure to thrive.

Older child with VKD can present with bruising, mucocutaneous bleeding or a more serious bleeding.

LAB Findings of VKD Abnormal findings Normal findings

Prothrombin time(PT) Partial thromboplastin time(PTT) Decreased levels of: II, VII, IX, X

BT, fibrinogen, platelets, factor5 and 8,

LAB Findings of VKD… Factor VII has the shortest half-life and is the first

to be affected by VKD.

In case of Mild VKD the PT is normal but there are elevated levels of uncarboxylated proteins known as the Proteins induced by vitamin k absence (PIVKA).

Measurement of PIVKA- II can detect mild VKD.

Measuring of blood vit-k is less useful because of significant variations based on dietary intake and blood levels do not always reflect tissue stores of vitamin K.

Diagnosis of VKD Dx of VKD is established by the presence of prolonged

PT that corrects rapidly after administration of vitamin K, which stops active bleeding.

Differential diagnosis of VKD Other possible causes of bleeding and prolonged PT

include:

DIC

Liver failure

Hereditary deficiency of clotting factors.

Vitamin C deficiency.

Differential diagnosis of VKD… In DIC mostly due to Sepsis there is consumption of

coagulation factors and Lab investigations shows thrombocytopenia, low fibrinogen and elevated D-dimers.

DIC is characterized by asphyxia, hypoxia, acidosis, shock and hemangiomas and infection.

Treatment is to correct the primary clinical problem such as infection and interrupt consumption of clotting factors and their replacement.

Differential diagnosis of VKD… In case of severe liver disorders like cirrhosis the

production of clotting factors is decreased and administration of vitamin k is not effective (PT may not correct with vitamin k).

Children with hereditary disorders have deficiency of specific factors.

Anticoagulants effects on vit-K Warfarin and cumarin derivatives inhibit the action of

vitamin k by preventing its recycling to an active form after it functions as a cofactor for gamma-glutamyl carboxylase.

Bleeding can occur with over dosage of warfarin and ingestion of rodent poison (rat poison) that contains a coumarin derivate

High doses of salisylate also inhibit regeneration of vitamin k and can cause prolongation of PT and clinical bleeding.

Anticoagulants effects on vit-K.. Warfarin prevents coagulation only in vivo and cannot

prevent coagulation of blood in vitro.

When warfarin is given to patient 2-3days are required to see its full anti-coagulant activity and so to prevent formation of thrombosis in these 3days we must heparinize the patient ,behind this there are two issues: Warfarin only acts in the liver to inhibit synthesis of the

next generation of the clotting factors, so to run out the already formed active clotting factors from blood we must heparinize the patient.

Treatment of VKD Acute VKDB is treated with 1mg/kg of parenteral

vitamin k(0.5-1.0mg/kg) in newborns.

After administration of vitamin k PT should decrease within 6hours and normalize within 24hours.

Older children with acute bleeding should receive 2.5-10mg vitamin k IM or IV.

In addition to vitamin k a Patient with severe and life-threatening bleeding should receive infusion of fresh-frozen plasma to correct the coagulapathy rapidly.

Treatment of VKD… In case of malabsorption chronic administration of

high doses of oral vitamin k(2.5mg twice/wk to 5mg/day) along with bile salts is required.

To reserve warfarin effects 25-50mg IV vitamin k1 (phytonadione which acts rapidly) is given.

If severe bleeding occurs 10mg IM followed by 5mg 4hourly is given with this bleeding stops in 6-12hrs but PT became normal in 24 hrs.

Prevention of VKD IM Administration of 1mg vitamin k soon after birth

prevents early VKDB.

Discontinuing the offending medication before delivery can prevent VKDB if this was not possible administration of 5-10mg IM vitamin k 4-12 hrs before delivery to mother may be helpful, in addition the neonate should receive IM injection of vitamin k immediately after birth and in severe cases use fresh-frozen plasma.

In malabsorption chronic supplementation of vitamin k and periodic measurement of PT is necessary.

Toxicity and adverse effects of vitamin k Fat-soluble vitamin has very low order of toxicity.

Water-soluble, synthetic vitamin k3 causes:

Vomiting

Porphyrinuria

Albuminuria

Hemolytic anemia

Hemoglubinuria

hyperbilirubinemia

Toxicity and adverse effects of vitamin k Rapid IV injection of emulsified vit K causes:

Flushing

Breathlessness

Chest constriction

Fall in B.P

Anaphylactic reaction

Hematomas at the site of IM injection.

Association between parenteral use of vitamin k at birth and later development of malignancy is not confirmed.

Vitamin K is also used for Anticoagulant drug overdose

Reduces excessive menstrual blood flow

Protection against osteoporosis

Prolonged treatment with broad-spectrum ABx antibiotics especially in ICU patients.

Obstructive jaundice, liver cirrhosis, viral hepatitis.

Prolonged high doses salisylate therapy .

Conclusion Vitamin k is the mainstay for prevention of and

treatment of vitamin k deficiency bleeding(VKDB).

Severe bleeding may warrant the use of fresh-frozen plasma.

Subcutaneous administration of vitamin k is preferred over IM route in symptomatic infants.

References NELSON TEXTBOOK OF PEDIATRICS 20E

medilibros.com_2.pdf

Current pediatrics Diagnosis and Treatment 18th edition

GHAI Essential Pediatrics, 8th edition

KAPLAN medical pediatrics lecture notes 2008-2009

www.Medscape.com

https://www.google.com.af/

www.slideshare.net/

https://studentconsult.inkling.com/

Prepared By:

Dr.mujeebullah Mahboob

1St year resident of Ped-Med

FMIC

Afghanistan, Kabul

19/10/2015

01:15pm

W_mahboob@yahoo.com

0798984142