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 which of the following?
The answer is: B
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
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.
Evaluation of a pedigree for a certain abnormality reveals the following information:
there are skipped generations with male-to-male transmission; females are affected at the
same rate as are males; and the disease is produced in the homozygous state, while
heterozygous individuals are carriers. What is the inheritance pattern for this disorder?