CASE HISTORY • Part 1
A 37-year-old woman presents to the emergency department with a swollen, tender left calf and dyspnea. She noted the development of symptoms 3 days ago, the day following her arrival on a plane trip from Australia to the United States. She admits to pleuritic chest pain but denies cough or fever, and has no significant past medical history. Her only medication is an oral contraceptive. She does not smoke cigarettes or use alcohol. Her parents are alive; her father takes a "blood thinner" medication for an unknown reason.
Examination reveals a diaphoretic white female with tachypnea; positive examination findings include an inspiratory friction rub on the left side of the chest, a swollen left calf with a circumference 50% greater than on the right, and a positive left Homans sign. Vital signs: BP - 100/60 mm Hg, pulse - 115 bpm, resp - 26/min, temp 38°C. Pulse oximetry shows O2 saturation on room air of 92%.
CBC: Hemoglobin/hematocrit - 13 g/dL/39%
MCV - 88 fL MCH - 31 pg MCHC - 32 g/dL
WBC count - 11,000/μL with normal differential
Platelet count - 310,000/μL
Troponin I <0.04 ng/mL (<0.04 ng/mL)
Pregnancy test - negative
PT = 12.1 seconds (<14 seconds)
PTT = 27 seconds (22–35 seconds)
D-dimer = 1,400 ng/mL (<500 ng/mL) Questions
Given this history and physical findings, what diagnosis must be considered?
Do the screening laboratory tests confirm this diagnosis?
If not, what further workup is indicated?
Abnormal thrombus formation and thromboembolism can occur secondary to a wide variety of diseases or as a primary hypercoagulable state. The pathophysiologic basis for thrombotic disease includes acquired abnormalities of blood vessels or blood flow, excessive production of thromboplastic substances as with localized tissue necrosis, and inherited abnormalities of coagulation factors. Thus, clinical evaluation of a patient with thrombotic disease involves both a search for a clinical condition that is known for its association with thrombosis or thromboembolism, and laboratory evaluation of the anticoagulant and fibrinolytic pathways.
NORMAL CONTROL OF THROMBUS FORMATION
Thrombus formation is normally limited by several physiologic systems. Excessive platelet aggregation is inhibited at the site of thrombosis by rapid dissipation of platelet stimulatory substances such as adenosine 5′-diphosphate (ADP), thromboxane A2, and thrombin and direct platelet inhibition by ADPase, prostacyclin, and nitric oxide produced by adjacent normal endothelial cells. Together, these inhibitors limit the size of the platelet thrombus and further activation of coagulation by platelets.
Fibrin clot formation is also controlled by several mechanisms, including antithrombin (AT) inhibition of thrombin, endothelial protein receptor/thrombomodulin-driven protein C/S inactivation of factors Va and VIIIa, tissue factor pathway inhibition, protein Z–dependent protease inhibitor, and fibrinolysis. As shown in Figure 36-1, tissue factor pathway inhibitor (TFPI) stops factor Xa activation of prothrombin by binding to the tissue factor (TF)–factor VIIa-Xa complex. This process acts to limit the procoagulant effect ...