Vitamin K Deficiency and Hemorrhage

Vitamin K found in green leafy vegetables

a fat soluble vitamin that requires bile salt for absorption

*Biliary duct obstruction (atresia), fat malabsorption, chronic diarrhea, and broad-spectrum antibiotics
can possibly cause vit. K deficiency

A. Hemorrhagic Disease of the Newborn Caused by Vitamin K Deficiency

Caused by their sterile intestines and the minimal conc. of vit. K in human milk.

Low activity levels of Factor II, VII, IX, and X.

Breastfeeding prolongs the deficiency because the passively acquired Abs delay the establishment of
gut flora.

B. Vitamin K. Antagonists: Coumadin

Coumadin (Warfarin) interrupts the -carboxylation of coagulation factor II, VII, IX, and X, and proteins
C,S, and Z (Prothrombin Group).

disrupts the vit. K epoxide reductase and vit. K quinone reductase reactions.

PIVKAs inactive forms of prothrombin group

Brodifacoum (superwarfarin) used as a rodenticide

poisoning of this requires treatment that lasts for weeks to months

Coumadin overdose the single most common reason for hemorrhage-associated emergency
department visits.

C. Detection of Vitamin K Deficiency or Proteins in Vitamin K Antagonism

*Prolonged PT w/normal or prolonged PTT

*Mixture of pooled platelet-free normal plasma and patient plasma yields normal (corrected) PT and
PTT results indicating that factor deficiencies were the cause of the prolonged screening test.

Specific single-factor assays always detect low factor VII (due to short half-life), IX, X, and II

Standard therapy oral intake or intravenous (in emergency situation)

3 hours minimum time required for synthesis of vit. K - dependent coagulation factors
PCC (rFVIIa) may be administered during severe bleeding

PT/INR can indirectly monitor patients recovery

Autoanti-VII Inhibitor and Acquired Hemophilia

Auto-anti VII most common acquired autoantibody

diagnostic of acquired hemophilia

patients are frequently older than 60

no apparent underlying disease

Acquired hemophilia occasionally associated w/ RA, inflammatory bowel disease, SLE, or

lymphoproliferative disease.

appears to be triggered by pregnancy 2 to 5 months after delivery

has an overall incidence of 1 per 1 million people per year

sudden and severe bleeding in soft tissues, in GIT and genitourinary tract.

Even when treated, has 20% fatality rate

A. Clot-Based Assays in Acquired Hemophilia

PT,PTT, and thrombin time test that are recommended for anatomic hemorrhage that resembles
acquired hemophilia.

Factor VIII inhibitor prolonged PTT (30% less activity), normal PT and thrombin time

PTT prolongation (clot-based mixing studies) confirmatory test

corrected initially by addition of normal plasma (NP) in

the specimen (1:1)

prolonged after incubation at 37C for 1 to 2 hrs.

Immunoglobulin G4 isotype Factor VIII autoantibodies

time and temperature dependent, responsible for the return prolongation

Type II kinetics The nonlinear neutralization of autoantibody. Although there is rapid loss of Factor VIII
activity, residual activity remains, which indicates that the reaction has reached equilibrium.

Type I kinetics The linear in vitro neutralization of factor VIII activity over 1 to 2 hours, which results in
complete inactivation.

Bethesda assay Quantitation of autoanti-VIII inhibitor

 Employed to measure inhibitors in hemophilic patients with alloantibodies to factor VIII.

B. Factor Inhibitors Other Than Autoanti-Factor VIII

Factor II antibodies (anti-prothrombin) Developed in 30% of patients with lupus anticoagulant

Patients experience bleeding and prolonged PT

Isoniazid Treatment for TB

Factor V and XIII inhibitors have been documented with this treatment

Antiboides to Factor IIa (Thrombin) & Factor V arise from exposure to topical bovine thrombin or fibrin
glue.

Autoanti-X antibodies cause Factor X deficiency

C. Acquired Hemophilia Management

Activated PCC (vFVIIa) may bypass the coagulation factor VIII inhibitor in acquired hemophilia abd
thereby control acute bleeding

D. Acquired Von Willebrand Disease

Acquired VWF deficiency symptoms similar to congenital VWD

manifests w/ moderate to severe mucocutaneous bleeding

normal PT, moderately prolonged PTT

cause Factor VIII deficiency

required for

Pathogenesis: decrease production of VWF, presence of an Ab, and adsorption of VWF to

abnormal cell surfaces.

DDAVP (Humate-P, Willate, Alphanate) required for treatment for bleeding

E. Disseminated Intravascular Coagulation

DIC Thrombotic disorder w/ hemorrhagic symptoms