MCQ6.
A 25-year-old female presents with a history of losing four pregnancies
in the past 5 years. She also has a history of recurrent pains in her legs secondary
to recurrent thrombosis. Her symptoms are most likely due to a
deficiency of
a. PA inhibitors
b. Protein C
c. Plasmin
d. Thrombin
e. C′1 inactivator
Answer The answer is b. (Henry, pp 726–727. Cotran, pp 122–126. Ayala, p
208.) Two important control points of the coagulation cascade are the fibrinolytic
system and certain plasma protease inhibitors. The main component
of the fibrinolytic system is plasmin, which is converted from
plasminogen by either factor XII or a plasminogen activator (PA). Examples
of PAs include tissue plasminogen activator (tPA), urokinase plasminogen
activator, and streptokinase. Once formed, plasmin splits fibrin and also
General Pathology Answers 83
degrades both fibrinogen and coagulation factors VIII and V. Plasma protease
inhibitors include antithrombin III and protein C. Antithrombin III in
the presence of heparin inhibits thrombin, XIIa, XIa, Xa, and IXa, while
protein C inhibits Va and VIIIa. The significance of these control mechanisms
is illustrated by the fact that abnormalities of these systems, such as
deficiencies of antithrombin III, protein C, or protein S, are associated with
hypercoagulable states and increased risk of thrombosis, as the main factors
leading to thrombosis include injury to endothelium, alterations in
blood flow, and hypercoagulability of the blood. Hypercoagulability may
be a primary (genetic) or secondary abnormality. Primary hypercoagulable
states include the previously mentioned deficiencies of antithrombin III,
protein C, or protein S. These deficiencies are associated with recurrent
thromboembolism in early adult life and recurrent spontaneous abortions
in women. The causes of secondary hypercoagulable states are numerous
and include severe trauma, burns, disseminated cancer, and pregnancy.
Lower risk factors for the development of secondary hypercoagulable states
include age, smoking, and obesity. Some patients with high titers of
autoantibodies against anionic phospholipids such as cardiolipin (the antibody
being called a lupus anticoagulant) have a high frequency of arterial
and venous thrombosis. To summarize, it is important to remember that
the differential diagnosis of recurrent spontaneous abortions in women
includes deficiencies of protein C and protein S, and the presence of the
lupus anticoagulant, which is part of the anti-phospholipid syndrome.
