Page 350 - Textbook of Pathology, 6th Edition

334 recover spontaneously. Treatment is directed at reducing the B. THROMBOCYTOSIS
level and source of autoantibodies and reducing the rate of Thrombocytosis is defined as platelet count in excess of
destruction of sensitised platelets. This is possible by 4,00,000/μl. While essential or primary thrombocytosis or
corticosteroid therapy, immunosuppressive drugs (e.g. thrombocythaemia is discussed under myeloproliferative
vincristine, cyclophosphamide and azathioprine) and disorders in the next chapter, secondary or reactive
splenectomy. Beneficial effects of splenectomy in chronic ITP thrombocytosis can occur following massive haemorrhage,
are due to both removal of the major site of platelet iron deficiency, severe sepsis, marked inflammation,
destruction and the major source of autoantibody synthesis. disseminated cancers, haemolysis, or following splenectomy.
Platelet transfusions are helpful as a palliative measure only Thrombocytosis causes bleeding or thrombosis but how it
in patients with severe haemorrhage. produces is not clearly known.
As such, transitory and secondary thrombocytisis does
Thrombotic Thrombocytopenic Purpura (TTP) and not require any separate treatment other than treating the
Haemolytic-Uraemic Syndrome (HUS) cause.
Thrombotic thrombocytopenic purpura (TTP) and haemo-
lytic-uraemic syndrome (HUS) are a group of thrombotic C. DISORDERS OF PLATELET FUNCTIONS
microangiopathies which are essentially characterised by Defective platelet function is suspected in patients who show
triad of thrombocytopenia, microangiopathic haemolytic anaemia skin and mucosal haemorrhages and have prolonged
and formation of hyaline fibrin microthrombi within the micro- bleeding time but a normal platelet count. These disorders
SECTION II
vasculature throughout the body. These are often fulminant may be hereditary or acquired.
and lethal disorders occurring in young adults. The intra-
vascular microthrombi are composed predominantly of Hereditary Disorders
platelets and fibrin. The widespread presence of these platelet Depending upon the predominant functional abnormality,
microthrombi is responsible for thrombocytopenia due to inherited disorders of platelet functions are classified into
increased consumption of platelets, microangiopathic haemo- the following 3 groups:
lytic anaemia and protean clinical manifestations involving
different organs and tissues throughout the body. 1. DEFECTIVE PLATELET ADHESION. These are as
under:
PATHOGENESIS. Unlike DIC, a clinicopathologically i) Bernard-Soulier syndrome is an autosomal recessive
related condition, activation of the clotting system is not the disorder with inherited deficiency of a platelet membrane
primary event in formation of microthrombi. TTP is initiated glycoprotein which is essential for adhesion of platelets to
by endothelial injury followed by release of von Willebrand vessel wall.
factor and other procoagulant material from endothelial cells,
leading to the formation of microthrombi. Trigger for the ii) In von Willebrand’s disease, there is defective platelet
endothelial injury comes from immunologic damage by adhesion as well as deficiency of factor VIII (page 336).
diverse conditions such as in pregnancy, metastatic cancer, 2. DEFECTIVE PLATELET AGGREGATION. In thromba-
high-doze chemotherapy, HIV infection, and mitomycin C. sthenia (Glanzmann’s disease), there is failure of primary
platelet aggregation with ADP or collagen due to inherited
CLINICAL FEATURES. The clinical manifestations of TTP deficiency of two of platelet membrane glycoproteins.
are due to microthrombi in the arterioles, capillaries and
venules throughout the body. Besides features of thrombo- 3. DISORDERS OF PLATELET RELEASE REACTION.
cytopenia and microangiopathic haemolytic anaemia, These disorders are characterised by normal initial
Haematology and Lymphoreticular Tissues
characteristic findings include fever, transient neurologic aggregation of platelets with ADP or collagen but the
deficits and renal failure. The spleen may be palpable. subsequent release of ADP, prostaglandins and 5-HT is
defective due to complex intrinsic deficiencies.
LABORATORY FINDINGS. The diagnosis can be made
from the following findings: Acquired Disorders
1. Thrombocytopenia. Acquired defects of platelet functions include the following
2. Microangiopathic haemolytic anaemia with negative clinically significant examples:
Coombs’ test. 1. ASPIRIN THERAPY. Prolonged use of aspirin leads to
3. Leucocytosis, sometimes with leukaemoid reaction. easy bruising and abnormal bleeding time. This is because
4. Bone marrow examination reveals normal or slightly aspirin inhibits the enzyme cyclooxygenase, and thereby
increased megakaryocytes accompanied with some suppresses the synthesis of prostaglandins which are
myeloid hyperplasia. involved in platelet aggregation as well as release reaction.
5. Diagnosis is, however, established by examination of The anti-platelet effect of aspirin is clinically applied in
biopsy (e.g. from gingiva) which demonstrates typical preventing major thromboembolic disease in recurrent
microthrombi in arterioles, capillaries and venules, myocardial infarction.
unassociated with any inflammatory changes in the vessel 2. OTHERS. Several other acquired disorders are associated
wall.
with various abnormalities in platelet functions at different