Page 347 - Textbook of Pathology, 6th Edition

plasma that contains all other coagulation factors except the source of frequent episodes of bleeding from the nose and 331
one to be measured. The unknown level of the factor activity gastrointestinal tract.
is compared with a standard control plasma with a known 2. Inherited disorders of connective tissue matrix. These
level of activity. Results are expressed as percentage of include Marfan’s syndrome, Ehlers-Danlos syndrome and
normal activity.
pseudoxanthoma elasticum, all of which have inherited
ii) Quantitative assays. The coagulation factors can be defect in the connective tissue matrix and, thus, have fragile
quantitatively assayed by immunological and other chemical skin vessels and easy bruising.
methods.
B. Acquired Vascular Bleeding Disorders
D. Investigation of Fibrinolytic System
Several acquired conditions are associated with vascular
Increased levels of circulating plasminogen activator are purpuras. These are as under:
present in patients with hyperfibrinolysis. Following
screening tests are done to assess these abnormalities in 1. Henoch-Schönlein purpura. Henoch-Schönlein or
fibrinolytic system: anaphylactoid purpura is a self-limited type of hyper-
1. Estimation of fibrinogen. sensitivity vasculitis occurring in children and young adults.
2. Fibrin degradation products (FDP) in the serum. Circulating immune complexes are deposited in the vessel CHAPTER 13
3. Ethanol gelation test. wall consisting of IgA, C3 and fibrin, and in some cases,
4. Euglobin or whole blood lysis time. properdin suggesting activation of alternate complement
More specific tests include: functional assays, immuno- pathway as the trigger event. The hypersensitivity vasculitis
logical assays by ELISA, and chromogenic assays of produces purpuric rash on the extensor surfaces of arms, legs
plasminogen activators, plasminogen, plasminogen activator and on the buttocks, as well as haematuria, colicky
inhibitor, and FDP. abdominal pain due to bleeding into the GIT, polyarthralgia
With this background knowledge on work up of a case and acute nephritis. In spite of these haemorrhagic features,
of haemostatic abnormality, we now turn to discuss the all coagulation tests are normal.
common specific haemorrhagic disorders under the 2. Haemolytic-uraemic syndrome. Haemolytic-uraemic
following headings: syndrome is a disease of infancy and early childhood in which
I. Haemostatic diatheses due to vascular disorders. there is bleeding tendency and varying degree of acute renal
II. Haemostatic diatheses due to platelet disorders. failure. The disorder remains confined to the kidney where
III. Coagulation disorders. hyaline thrombi are seen in the glomerular capillaries.
IV. Haemostatic diatheses due to fibrinolytic defects. 3. Simple easy bruising (Devil’s pinches). Easy bruising
V. Disseminated intravascular coagulation (DIC) of unknown cause is a common phenomenon in women of
child-bearing age group.
HAEMORRHAGIC DIATHESES DUE TO
VASCULAR DISORDERS 4. Infection. Many infections cause vascular haemorrhages
either by causing toxic damage to the endothelium or by DIC.
Vascular bleeding disorders, also called non-thrombo- These are especially prone to occur in septicaemia and severe
cytopenic purpuras or vascular purpuras, are normally mild measles.
and characterised by petechiae, purpuras or ecchymoses 5. Drug reactions. Certain drugs form antibodies and Disorders of Platelets, Bleeding Disorders and Basic Transfusion Medicine
confined to the skin and mucous membranes. The produce hypersensitivity (or leucocytoclastic) vasculitis
pathogenesis of bleeding is poorly understood since majority responsible for abnormal bleeding.
of the standard screening tests of haemostasis including the
bleeding time, coagulation time, platelet count and platelet 6. Steroid purpura. Long-term steroid therapy or Cushing’s
function, are usually normal. Vascular purpuras arise from syndrome may be associated with vascular purpura due to
damage to the capillary endothelium, abnormalities in the defective vascular support.
subendothelial matrix or extravascular connective tissue that 7. Senile purpura. Atrophy of the supportive tissue of
supports the blood vessels, or from formation of abnormal cutaneous blood vessels in old age may cause senile atrophy,
blood vessels. especially in the dorsum of forearm and hand.
Vascular bleeding disorders may be inherited or acquired.
8. Scurvy. Deficiency of vitamin C causes defective colla-
gen synthesis which causes skin bleeding as well as bleeding
A. Inherited Vascular Bleeding Disorders
into muscles, and occasionally into the gastrointestinal and
A few examples of hereditary vascular disorders are given genitourinary tracts.
below:
HAEMORRHAGIC DIATHESES DUE TO
1. Hereditary haemorrhagic telangiectasia (Osler-Weber- PLATELET DISORDERS
Rendu disease). This is an uncommon inherited autosomal
dominant disorder. The condition begins in childhood and Disorders of platelets produce bleeding disorders by one of
is characterised by abnormally telangiectatic (dilated) the following 3 mechanisms:
capillaries. These telangiectasias develop particularly in the A. Due to reduction in the number of platelets i.e. various forms
skin, mucous membranes and internal organs and are the of thrombocytopenias.