Page 235 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 8-12 Nutritional and Metabolic Diseases

POTENTIAL CLINICAL CONSEQUENCES OF WARFARIN USE

Warfarin-induced skin necrosis manifesting
with purple hemorrhagic bullae and ulceration,
typically over fatty tissue

VITAMIN K DEFICIENCY
AND VITAMIN K ANTAGONISTS

Vitamin K is an essential nutrient that is required as a
cofactor for the production of a handful of coagulation
cascade proteins. It is a fat-soluble vitamin that is effi-
ciently stored in the human body. Vitamin K deficiency
is rare and is typically seen only transiently in neonates
and infants during the first 6 months of life. Affected
neonates may show abnormally prolonged bleeding
after minor trauma. Patients may have an elevated pro-
thrombin time (PT) and decreased serum levels of
vitamin K and coagulation factors. Therapy consists of
replacement of vitamin K to normal levels and a search Vitamin K
for any possible underlying cause, such as liver or gas-
trointestinal disease. Neonatal and infantile vitamin K Coumadin anticoagulants
deficiency is most likely caused by maternal breast milk produce vitamin K
deficiency.
insufficiency of vitamin K.
Vitamin K deficiency is rarely seen in adults, because
most diets contain enough vitamin K for normal physi-
ological functioning. Adult patients with liver disease
and malabsorption states are at highest risk for the Inactive Active Purple toe syndrome associated
development of vitamin K deficiency. Vitamin K may K K with vitamin K antagonist therapy
be found in two natural forms: vitamin K 1 (phylloqui-
none) and vitamin K 2 (menaquinone). K 1 is found in
plants, and K 2 is produced by various bacteria that make
up the normal flora of the gastrointestinal tract. Anti- Circulatory
biotics may cause a decrease in the bacterial production system
of vitamin K 2 , resulting in a lack of vitamin K available
for absorption. This is typically not a clinical issue
unless the patient is taking a vitamin K antagonist such
as warfarin. Vitamin K is absorbed in the distal jejunum
and ileum via passive diffusion across the cell mem-
brane. The majority of vitamin K is stored normally in
the liver. There, the vitamin is converted to its active
state, hydroxyquinone. An efficient vitamin K salvage
pathway normally prevents an individual from becom-
ing deficient in the vitamin. The enzyme vitamin K
epoxide reductase is responsible for converting the
inactive epoxiquinone to the active hydroxyquinone
form of vitamin K.
Warfarin is a synthetic analogue of vitamin K and is
the main vitamin K antagonist. It is indicated for use as
an anticoagulant in the treatment of a number of condi-
tions, including atrial fibrillation and deep venous
thrombosis, and after heart valve replacement surgery. Intracranial hemorrhage, after trauma, in the occipital
Warfarin acts by inhibiting the enzymes that are lobe in a patient taking warfarin
responsible for carboxylation of glutamate residues and
epoxide reductase. This both decreases the available
clotting factors and induces vitamin K deficiency,
leading to added reduction of available clotting factors.
Clinical Findings: Vitamin K antagonists have been initially develops small, red to violaceous petechiae and within 5 to 7 days after the initiation of warfarin therapy.
shown to cause a specific type of cutaneous eruption macules preceded by paresthesias. These regions Secondary infection may be a cause of significant mor-
known as warfarin necrosis, which occurs in approxi- become erythematous and purple (ecchymoses) with bidity. The affected areas continue to undergo necrosis
mately 0.05% of patients taking the medication. War- intense edematous skin. The lesions eventually ulcerate unless the warfarin is withheld and the patient is treated
farin necrosis affects the areas of the body that have or form hemorrhagic bullae. The hemorrhagic bullae with a different class of anticoagulant. The feet and
increased body fat, such as the breasts, the abdominal desquamate, leaving deep ulcers. Painful cutaneous lower extremities may have a reticulated, purplish dis-
pannus, and the thighs. The feet are also particularly ulcers may occur, with some extending into the subcu- coloration called “purple toe syndrome.” This cutane-
prone to development of warfarin necrosis. The skin taneous tissue, including muscle. Most ulcers appear ous drug reaction can be eliminated or at least drastically

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 221