BLEEDING DISORDERS

VITAMIN K DEFICIENCY BLEEDING

Faculty of Medicine University of Brawijaya

Clinical Competencies
Be able to describe: - the pathophysiology of vitamin K deficiency bleeding (VKDB) - the maternal and newborn causes of VKDB - the classification of VKDB - the management of VKDB Be able to diagnose VKDB based on clinical features and laboratory findings

Faculty of Medicine
University of Brawijaya

Pathophysiology
Vitamin K is a fat-soluble vitamin that can be absorbed from the GI tract in the presence of bile salts. Vitamin K is required for the production of coagulation FII, FVII, FIX and FX in the liver. Because of the short half-life of these factors, and the small amounts of vitamin K that can be stored in the body, inadequate intake of vitamin K can result in deficiency in a short period of time.

Faculty of Medicine
University of Brawijaya

Coagulation cascade
Intrinsic system (surface contact) XII XI XIIa XIa Extrinsic system (tissue damage) Tissue factor

IX VIII VIIIa

IXa

VIIa

VII

X
V
Vitamin K dependant factors

Xa Va

II
Faculty of Medicine
University of Brawijaya

IIa

(Thrombin)
Fibrin

Fibrinogen

Maternal Causes
An unhealthy diet or a malabsorption disorder: foods that have been irradiated/contain dioxin Not nursing long enough or frequently enough. Breast milk contains small amounts of Vitamin K Medications during pregnancy: cephalosporin, anti TB drugs, anticoagulants, anticonvulsants, barbiturates, chemotherapy, radiation, chemical vapors (dioxin), aspirin, sulfa and iodine Maternal diabetes, toxemia, or placental problems Undue stress during the pregnancy can affect how well the babys liver functions.

Faculty of Medicine
University of Brawijaya

Newborn Causes
Poor feeding or not nursing enough. GI disease or homeostasis (blockage of bile drainage ducts in the liver, caused by hepatitis, undeveloped bile ducts or other congenital defects, or infection). Prolonged, pronounced jaundice is a sign of these. Mothers medications during the pregnancy or labor, or that the baby has been given as a newborn. A difficult birth, resulting in birth trauma. Prematurity: the immature liver functions Hypoxia (lack of oxygen). Diarrhea > 3 days.

Faculty of Medicine
University of Brawijaya

Classification
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
Faculty of Medicine
University of Brawijaya

Early VKDB
Onset < 24 hours of age Early VKDB is rare. The incidence in newborns of mothers taking these drugs without VK supplementation varies 6 - 12%. It is due to placental transfer of maternal drugs which inhibit vitamin K-activity in the baby: anticonvulsants (carbamazepine, phenytoin & barbiturates), cephalosporins, tuberculostatic agents (rifampicin, INH) & VK antagonists (phenprocoumon, warfarin).

Faculty of Medicine
University of Brawijaya

Classical VKDB
Begins in the 1st week excluding the first 24 hours, usually between days 3 and 5 and in babies with delayed or inadequate feeding. Frequency: 0 - 0.44% in recent reviews. Bleeding is usually from the umbilicus, GI tract & skin punctures may cause significant blood loss. ICH is rare but can cause significant morbidity or death.

Faculty of Medicine
University of Brawijaya

Late VKDB
Begins on or after day 8, most often between weeks 2 and 8 and rarely after 3 months; occurs almost exclusively in breast-fed infants, in boys > girls. Have signs of predisposing disease (e.g. prolonged jaundice with pale stools and dark urine implying cholestasis, or failure to thrive suggesting malabsorption) long before bleeding begins. Have warning bleeds e.g. mild bruises, nose bleeds or umbilical oozing as the first manifestation of VKDB, followed (sometimes days later) by ICH.

Faculty of Medicine
University of Brawijaya

Table 1. Forms of VKDB in Infancy

Faculty of Medicine
University of Brawijaya

Clinical Features
Bleeding at any site (spontaneous or iatrogenic). The common sites for spontaneous bleeding: umbilicus, mucous membranes, skin, GI & urinary tract, and retroperitoneum. Hematomas at sites of trauma: large cephalohematomas and bruising (common findings). Iatrogenic causes: the abnormal bleeding is precipitated by venepuncture or surgery. ICH can occur and is the main cause of mortality & longterm morbidity.

Faculty of Medicine
University of Brawijaya

Laboratory Findings
A prolonged PT In practice, a clearly prolonged PT [International Normalized Ratio (INR) >3.5] with normal fibrinogen & platelet count is highly suggestive of VKD. Rapid normalization (within 30-120 min) or PT value after administration of VK is diagnostic. Vitamin K direct assay is not useful because levels normally are low in newborns. Levels of protein induced by vitamin K antagonism (PIVKA) II in VKDB not available

Faculty of Medicine
University of Brawijaya

Management
Treatment Vitamin K1: 1 mg once daily IM/SC/IV for 3 days. Severe bleeding: fresh frozen plasma (FFP) 10 ml/kg/day

Prevention Vit. K 1 mg IM at birth: effective in preventing late VKDB Vit. K 1 mg orally at interval of up to 5 weeks can protects newborns from the classical form of VKDB and the recurrence of late VKDB

Faculty of Medicine
University of Brawijaya

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. This may effect changes at the cellular level. Jaundice: babys liver must process the shot; causes rise in bilirubin. Bleeding may still occur. One shot may not protect the baby from VKDB. Anaphylactic shock, allergy to preservative in shot. Trauma at injection site (pain, swelling).

Faculty of Medicine
University of Brawijaya

MODUL TASK
1. Describe in brief the causes and pathophysiology of VKDB ! 2. Describe in brief classification of VKDB by causes and age at onset ! 3. Describe clinical features and laboratory findings to diagnose VKDB ! 4. Describe the management (treatment and prevention) of VKDB !

5. Describe risks of giving the prophylactic vitamin K shot to the baby !

Faculty of Medicine
University of Brawijaya

Faculty of Medicine
University of Brawijaya