Overview of Thrombotic Disorders

Genetic defects that increase the propensity for venous thromboembolism include

Protein Z, a vitamin K-dependent protein, helps inactivate coagulation factor Xa. Deficiency or dysfunction of protein Z Protein Z Deficiency Because protein Z helps inactivate coagulation factor Xa, deficiency or dysfunction of protein Z predisposes to venous thrombosis (mainly in patients who also have other clotting abnormalities)... read more predisposes to venous thrombosis (mainly in patients who also have other clotting abnormalities). However, measurement of its activity is not available in most laboratories.

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

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 Superficial Venous Thrombosis Superficial venous thrombosis is a blood clot in a superficial vein of the upper or lower extremities or, less commonly, in one or more veins of the chest or breast (Mondor disease). Superficial... read more 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. Diagnosis is by pelvic examination, measurement of beta subunit of human chorionic gonadotropin, and ultrasonography. Treatment... read more .

Diagnostic evaluations of thrombotic disorders 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. For patients requiring hospitalization, anticoagulation typically is started with unfractionated heparin or low molecular weight heparin (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 ). For patients who can be treated as outpatients, direct oral anticoagulants (DOACs) or warfarin is used (1, 2, 3 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 ).

DOACs include factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) and the direct thrombin inhibitor dabigatran. Unlike warfarin, DOACs do not require regular laboratory monitoring, and some of these medications (apixaban, rivaroxaban) can be used in acute treatment without initial parenteral anticoagulation. In contrast to warfarin, DOACs have fewer drug-drug interactions and their effectiveness is not influenced by diet.

In the event of life-threatening bleeding, reversal agents for DOACs include targeted antidotes (idarucizumab for dabigatran; andexanet alfa for the factor Xa inhibitors) as well as non-specific prohemostatic agents such as prothrombin complex concentrates which contain factors VII, IX, X, and prothrombin (1, 4, 5 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 ]. Warfarin is reversed with vitamin K and prothrombin complex concentrates.

A major current disadvantage of DOACs is their expense.