Page 622 - Basic _ Clinical Pharmacology ( PDFDrive )

34 Drugs Used in Disorders
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of Coagulation

James L. Zehnder, MD

C ASE STUD Y

A 25-year-old woman presents to the emergency depart- and edema and is tender to touch. Oxygen saturation by
ment complaining of acute onset of shortness of breath and fingertip pulse oximeter while breathing room air is 87%
pleuritic pain. She had been in her usual state of health until (normal > 90%). Ultrasound reveals a deep vein thrombosis
2 days prior when she noted that her left leg was swollen and in the left lower extremity; chest computed tomography scan
red. Her only medication was oral contraceptives. Family confirms the presence of pulmonary emboli. Laboratory
history was significant for a history of “blood clots” in mul- blood tests indicate elevated d-dimer levels. What therapy
tiple members of the maternal side of her family. Physical is indicated acutely? What are the long-term therapy
examination demonstrates an anxious woman with stable options? How long should she be treated? Should this indi-
vital signs. The left lower extremity demonstrates erythema vidual use oral contraceptives?

Hemostasis refers to the finely regulated dynamic process of main- MECHANISMS OF BLOOD
taining fluidity of the blood, repairing vascular injury, and limit- COAGULATION
ing blood loss while avoiding vessel occlusion (thrombosis) and
inadequate perfusion of vital organs. Either extreme—excessive The vascular endothelial cell layer lining blood vessels has an
bleeding or thrombosis—represents a breakdown of the hemo- anticoagulant phenotype, and circulating blood platelets and
static mechanism. Common causes of dysregulated hemostasis clotting factors do not normally adhere to it to an appreciable
include hereditary or acquired defects in the clotting mechanism extent. In the setting of vascular injury, the endothelial cell layer
and secondary effects of infection or cancer. Atrial fibrillation is rapidly undergoes a series of changes resulting in a more proco-
associated with stasis of blood in the atria, formation of clots, and agulant phenotype. Injury exposes reactive subendothelial matrix
increased risk of occlusive stroke. Because of the high prevalence proteins such as collagen and von Willebrand factor, which
of chronic atrial fibrillation, especially in the older population, results in platelet adherence and activation, and secretion and
use of anticoagulants is common. Guidelines for the use of oral synthesis of vasoconstrictors and platelet-recruiting and activating
anticoagulants (CHA DS -VASC score, see January C et al refer- (TXA ) is synthesized from
2
2
ence) are based on various risk factors (congestive heart failure, molecules. Thus, thromboxane A 2 2
arachidonic acid within platelets and is a platelet activator and
hypertension, age, diabetes, history of stroke, vascular disease, potent vasoconstrictor. Products secreted from platelet granules
and sex). The drugs used to inhibit thrombosis and to limit abnor- include adenosine diphosphate (ADP), a powerful inducer of
mal bleeding are the subjects of this chapter. platelet aggregation, and serotonin (5-HT), which stimulates

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