Page 353 - Textbook of Pathology, 6th Edition

of coagulation such as antithrombin III and protein C and S At times, it may be difficult to distinguish primary 337
and plays a role in the clearance of activated factors and pathologic fibrinolysis from secondary fibrinolysis
fibrinolytic enzymes. Thus, patients with liver disease may accompanying DIC.
develop hypercoagulability and are predisposed to develop
DIC and systemic fibrinolysis. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
The major causes of bleeding in liver diseases are as
under: Disseminated intravascular coagulation (DIC), also termed
defibrination syndrome or consumption coagulopathy, is a
A. Morphologic lesions: complex thrombo-haemorrhagic disorder (intravascular
1. Portal hypertension e.g. varices, splenomegaly with coagulation and haemorrhage) occurring as a secondary
secondary thrombocytopenia. complication in some systemic diseases.
2. Peptic ulceration. ETIOLOGY. Although there are numerous conditions
3. Gastritis. associated with DIC, most frequent causes are listed below:
B. Hepatic dysfunctions: 1. Massive tissue injury: in obstetrical syndromes (e.g.
1. Impaired hepatic synthesis of coagulation factors. abruptio placentae, amniotic fluid embolism, retained dead
foetus), massive trauma, metastatic malignancies, surgery.
2. Impaired hepatic synthesis of coagulation inhibitors: CHAPTER 13
protein C, protein S and antithrombin III. 2. Infections: especially endotoxaemia, gram-negative and
meningococcal septicaemia, certain viral infections, malaria,
3. Impaired absorption and metabolism of vitamin K. aspergillosis.
4. Failure to clear activated coagulation factors causing DIC 3. Widespread endothelial damage: in aortic aneurysm,
and systemic fibrinolysis.
haemolytic-uraemic syndrome, severe burns, acute
C. Complications of therapy: glomerulonephritis.
1. Following massive transfusion leading to dilution of 4. Miscellaneous: snake bite, shock, acute intravascular
platelets and coagulation factors. haemolysis, heat stroke.
2. Infusion of activated coagulation proteins. PATHOGENESIS. Although in each case, a distinct trig-
3. Following heparin therapy. gering mechanism has been identified, the sequence of
Many a times, the haemostatic abnormality in liver events, in general, can be summarised as under (Fig. 13.7):
disease is complex but most patients have prolonged PT and 1. Activation of coagulation. The etiologic factors listed
PTTK, mild thrombocytopenia, normal fibrinogen level and above initiate widespread activation of coagulation pathway
decreased hepatic stores of vitamin K. by release of tissue factor.
2. Thrombotic phase. Endothelial damage from the various
HAEMORRHAGIC DIATHESIS DUE TO
FIBRINOLYTIC DEFECTS thrombogenic stimuli causes generalised platelet aggregation
and adhesion with resultant deposition of small thrombi and
Normally, fibrinolysis consisting of plasminogen-plasmin emboli throughout the microvasculature.
and fibrin degradation products (FDPs) is an essential 3. Consumption phase. The early thrombotic phase is
protective physiologic mechanism to limit the blood followed by a phase of consumption of coagulation factors
coagulation in the body. However, unchecked and excessive and platelets. Disorders of Platelets, Bleeding Disorders and Basic Transfusion Medicine
fibrinolysis may sometimes be the cause of bleeding. The 4. Secondary fibrinolysis. As a protective mechanism,
causes of primary pathologic fibrinolysis leading to fibrinolytic system is secondarily activated at the site of
haemorrhagic defects are as under: intravascular coagulation. Secondary fibrinolysis causes
1. Deficiency of α -plasmin inhibitor following trauma or breakdown of fibrin resulting in formation of FDPs in the
2
surgery. circulation.
2. Impaired clearance of tissue plasminogen activator such Pathophysiology of DIC is summed up schematically in
as in cirrhosis of liver. Fig. 13.8.

Figure 13.7 The pathogenesis of disseminated intravascular coagulation.