Overview of Thrombotic Disorders

Genetic defects that increase the propensity for venous thromboembolism include

Acquired defects also predispose to venous and arterial thrombosis (see table Acquired Causes of Thromboembolism Acquired Causes of Thromboembolism ).

Other disorders and environmental factors can increase the risk of thrombosis, especially if a genetic abnormality is also present.

Common manifestations of a thrombotic disorder include unexplained deep venous thrombosis Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more and pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more (PE). Superficial thrombophlebitis can also develop. Other consequences may include arterial thrombosis (eg, causing stroke Ischemic Stroke Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes... read more or mesenteric ischemia Acute Mesenteric Ischemia Acute mesenteric ischemia is interruption of intestinal blood flow by embolism, thrombosis, or a low-flow state. It leads to mediator release, inflammation, and ultimately infarction. Abdominal... read more ). Symptoms depend on the location of the clot, as in the following examples:

Most of the inherited disorders do not begin to cause an increased risk of clotting until young adulthood, although clots can form at any age. Women may have a history of multiple spontaneous abortions Spontaneous Abortion Spontaneous abortion is pregnancy loss before 20 weeks gestation. Threatened abortion is vaginal bleeding without cervical dilation before 20 weeks in a confirmed viable intrauterine pregnancy... read more .

Diagnoses are summarized elsewhere in THE MANUAL specific to the location of the thrombus (eg, deep venous thrombosis Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more , pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more , ischemic stroke Ischemic Stroke Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes... read more ). Patients who have a thromboembolic event in the absence of an overt clinical explanation may have one of the genetic or acquired predisposing entities described below. It is often valuable to enlist the input of a hematologist in order to sort out the daunting array of diagnostic possibilities.

Treatment is summarized elsewhere in THE MANUAL specific to the location of the thrombus.

Anticoagulation is often required, typically beginning with parenteral heparin or low molecular weight heparin, and then followed by oral warfarin or one of the direct oral anticoagulants (DOACs). Drugs include factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) and a direct thrombin inhibitor (dabigatran). Unlike warfarin, the direct oral anticoagulants do not require regular laboratory monitoring. DOACs can be reversed either by time (they have brief in vivo half-lives) or in some cases by recently developed agents (idaricizumab for dabigatran; andexanet for rivaroxaban or apixaban [ 1, 2 Treatment references In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more ]).

A major current disadvantage of DOACs is their expense.