Page 352 - Textbook of Pathology, 6th Edition

336 TREATMENT. Symptomatic patients with bleeding Type I disease is the most common and is characterised by
episodes are treated with factor VIII replacement therapy, mild to moderate decrease in plasma vWF (50% activity).
consisting of factor VIII concentrates or plasma cryo- The synthesis of vWF is normal but the release of its
precipitates. With the availability of this treatment, the life multimers is inhibited.
expectancy of even severe haemophilic patients was approa- Type II disease is much less common and is characterised
ching normal but the occurrence of AIDS in multitransfused by normal or near normal levels of vWF which is functionally
haemophilic patients has adversely affected the life defective.
expectancy.
Type III disease is extremely rare and is the most severe
Christmas Disease (Haemophilia B) form of the disease. These patients have no detectable vWF
activity and may have sufficiently low factor VIII levels.
Inherited deficiency of factor IX (Christmas factor or plasma Bleeding episodes in vWD are treated with cryo-
thromboplastin component) produces Christmas disease or precipitates or factor VIII concentrates.
haemophilia B. Haemophilia B is rarer than haemophilia A;
its estimated incidence is 1 in 100,000 male births. The LABORATORY FINDINGS. These are as under:
inheritance pattern and clinical features of factor IX deficiency 1. Prolonged bleeding time.
are indistinguishable from those of classic haemophilia but 2. Normal platelet count.
accurate laboratory diagnosis is critical since haemophilia B 3. Reduced plasma vWF concentration.
requires treatment with different plasma fraction. The usual 4. Defective platelet aggregation with ristocetin, an
screening tests for coagulation are similar to those in classic antibiotic.
SECTION II
haemophilia but bioassay of factor IX reveals lowered 5. Reduced factor VIII activity.
activity.
TREATMENT. Therapy in symptomatic haemophilia B Vitamin K Deficiency
consists of infusion of either fresh frozen plasma or a plasma Vitamin K is a fat-soluble vitamin which plays important
enriched with factor IX. Besides the expected possibilities of role in haemostasis since it serves as a cofactor in the
complications of hepatitis, chronic liver disease and AIDS,
the replacement therapy in factor IX deficiency may activate formation of 6 prothrombin complex proteins (vitamin K-
dependent coagulation factors) synthesised in the liver: factor
the coagulation system and cause thrombosis and embolism.
II, VII, IX, X, protein C and protein S. Vitamin K is obtained
from green vegetables, absorbed in the small intestine and
von Willebrand’s Disease
stored in the liver (Chapter 9). Some quantity of vitamin K is
DEFINITION AND PATHOGENESIS. von Willebrand’s endogenously synthesised by the bacteria in the colon.
disease (vWD) is the most common hereditary coagulation Vitamin K deficiency may present in the newborn or in
disorder occurring due to qualitative or quantitative defect subsequent childhood or adult life:
in von Willebrand’s factor (vWF). Its incidence is estimated Neonatal vitamin K deficiency. Deficiency of vitamin K
to be 1 in 1,000 individuals of either sex. The vWF comprises in the newborn causes haemorrhagic disease of the newborn.
the larger fraction of factor VIII-vWF complex which Liver cell immaturity, lack of gut bacterial synthesis of the
circulates in the blood. Though the two components of factor vitamin and low quantities in breast milk, all contribute to
VIII-vWF complex circulate together as a unit and perform vitamin K deficiency in the newborn and may cause
the important function in clotting and facilitate platelet haemorrhage on 2nd to 4th day of life. Routine administration
adhesion to subendothelial collagen, vWF differs from factor of vitamin K to all newly born infants has led to
Haematology and Lymphoreticular Tissues
VIII in the following respects: disappearance of neonatal vitamin K deficiency.
1. The gene for vWF is located at chromosome 12, while that Vitamin K deficiency in children and adult. There are 3
of factor VIII is in X-chromosome. Thus, vWD is inherited as major causes of vitamin K deficiency in childhood or adult
an autosomal dominant trait which may occur in either sex, life:
while factor VIII deficiency (haemophilia A) is a sex (X-)- 1. Inadequate dietary intake.
linked recessive disorder. 2. Intestinal malabsorption.
2. The vWF is synthesised in the endothelial cells, mega- 3. Loss of storage site due to hepatocellular disease.
karyocytes and platelets but not in the liver cells, while the With the onset of vitamin K deficiency, the plasma levels
principal site of synthesis of factor VIII is the liver. of all the 6 vitamin K-dependent factors (prothrombin
3. The main function of vWF is to facilitate the adhesion of complex proteins) fall. This, in turn, results in prolonged PT
platelets to subendothelial collagen, while factor VIII is and PTTK. Parenteral administration of vitamin K rapidly
involved in activation of factor X in the intrinsic coagulation restores vitamin K levels in the liver.
pathway.
Coagulation Disorders in Liver Disease
CLINICAL FEATURES. Clinically, the patients of vWD are
characterised by spontaneous bleeding from mucous Since liver is the major site for synthesis and metabolism of
membranes and excessive bleeding from wounds. There are coagulation factors, liver disease often leads to multiple
3 major types of vWD: haemostatic abnormalities. The liver also produces inhibitors