Page 351 - Textbook of Pathology, 6th Edition

levels. These include: uraemia, liver disease, multiple mother passing on the abnormality to her children is 50:50 335
myeloma, Waldenström’s macroglobulinaemia and various for each son and 50:50 for each daughter. A haemophilic
myeloproliferative disorders. father will have normal sons as they inherit his Y chromo-
some only that does not carry the genetic abnormality.
COAGULATION DISORDERS The disease has been known since ancient times but
The physiology of normal coagulation is described in Chapter Schönlein in 1839 gave this bleeder’s disease its present name
5 together with relatively more common coagulation haemophilia. In 1952, it was found that haemophilia was not
disorders of arterial and venous thrombosis and embolism. always due to deficiency of factor VIII as was previously
A deficiency of each of the thirteen known plasma considered but instead blood of some patients was deficient
coagulation factors has been reported, which may be in factor IX (Christmas factor or plasma thromboplastin
inherited or acquired. In general, coagulation disorders are component). Currently, haemophilia A (classic haemophilia) is
less common as compared with other bleeding disorders. The the term used for the disorder due to factor VIII deficiency,
type of bleeding in coagulation disorders is different from and haemophilia B (Christmas disease) for the disorder when
that seen in vascular and platelet abnormalities. Instead of factor IX is deficient.
spontaneous appearance of petechiae and purpuras, the The frequency of haemophilia varies in different races,
plasma coagulation defects manifest more often in the form the highest incidence being in populations of Britain, CHAPTER 13
of large ecchymoses, haematomas and bleeding into muscles, Northern Europe and Australia. Western literature reports
joints, body cavities, GIT and urinary tract. For establishing give an overall incidence of haemophilia in 1 in 10,000 male
the diagnosis, screening tests for coagulation (whole blood births. Another interesting facet of the haemophilia which
coagulation time, bleeding time, activated partial has attracted investigators and researchers is the occurrence
thromboplastin time and prothrombin time) are carried out, of this disorder in the blood of royal families in Great
followed by coagulation factor assays as discussed already on Britain and some European countries.
page 330. PATHOGENESIS. Haemophilia A is caused by quantitative
Disorders of plasma coagulation factors may have here- reduction of factor VIII in 90% of cases, while 10% cases have
ditary or acquired origin.
normal or increased level of factor VIII with reduced activity.
HEREDITARY COAGULATION DISORDERS. Most of the Factor VIII is synthesised in hepatic parenchymal cells and
inherited plasma coagulation disorders are due to qualitative regulates the activation of factor X in intrinsic coagulation
or quantitative defect in a single coagulation factor. Out of pathway. Factor VIII circulates in blood complexed to another
defects in various coagulation factors, two of the most larger protein, von Willebrand’s factor (vWF), which
common inherited coagulation disorders are the sex-(X)- comprises 99% of the factor VIII-vWF complex. The genetic
linked disorders—classic haemophilia or haemophilia A (due to coding, synthesis and functions of vWF are different from
inherited deficiency of factor VIII), and Christmas disease or those of factor VIII and are considered separately below
haemophilia B (due to inherited deficiency of factor IX). under von Willebrand’s disease. Normal haemostasis
Another common and related coagulation disorder, von requires 25% factor VIII activity. Though occasional patients
Willebrand’s disease (due to inherited defect of von with 25% factor VIII level may develop bleeding, most
Willebrand’s factor), is also discussed here. symptomatic haemophilic patients have factor VIII levels
ACQUIRED COAGULATION DISORDERS. The acquired below 5%.
coagulation disorders, on the other hand, are usually CLINICAL FEATURES. Patients of haemophilia suffer from Disorders of Platelets, Bleeding Disorders and Basic Transfusion Medicine
characterised by deficiencies of multiple coagulation factors. bleeding for hours or days after the injury. The clinical
The most common acquired clotting abnormalities are: severity of the disease correlates well with plasma level of
vitamin K deficiency, coagulation disorder in liver diseases, factor VIII activity. Haemophilic bleeding can involve any
fibrinolytic defects and disseminated intravascular organ but occurs most commonly as recurrent painful
coagulation (DIC). haemarthroses and muscle haematomas, and sometimes as
The more common of the hereditary and acquired haematuria. Spontaneous intracranial haemorrhage and
coagulation disorders are discussed below. oropharyngeal bleeding are rare, but when they occur they
are the most feared complications.
Classic Haemophilia (Haemophilia A)
LABORATORY FINDINGS. The following tests are
Classic haemophilia or haemophilia A is the second most abnormal:
common hereditary coagulation disorder next to von 1. Whole blood coagulation time is prolonged in severe
Willebrand’s disease occurring due to deficiency or reduced cases only.
activity of factor VIII (anti-haemophilic factor). The disorder 2. Prothrombin time is usually normal.
is inherited as a sex-(X-) linked recessive trait and, therefore, 3. Activated partial thromboplastin time (APTT or PTTK)
manifests clinically in males, while females are usually the is typically prolonged.
carriers. However, occasional women carriers of haemophilia
may produce factor VIII levels far below 50% and become 4. Specific assay for factor VIII shows lowered activity.
symptomatic carriers, or rarely there may be true female The diagnosis of female carriers is made by the findings of
haemophilics arising from consanguinity within the family about half the activity of factor VIII, while the manifest
(i.e. homozygous females). The chances of a proven carrier disease is associated with factor VIII activity below 25%.