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Overview of Thrombotic Disorders


Joel L. Moake

, MD, Baylor College of Medicine

Last full review/revision Jan 2021| Content last modified Jan 2021
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In healthy people, homeostatic balance Overview of Hemostasis Hemostasis, the arrest of bleeding from an injured blood vessel, requires the combined activity of Vascular factors Platelets Plasma coagulation factors Regulatory mechanisms counterbalance... read more exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip the balance in favor of coagulation, leading to the pathologic formation of thrombi in veins (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 Deep Venous Thrombosis (DVT) [DVT]), arteries (eg, myocardial infarction Acute Myocardial Infarction (MI) Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and diaphoresis.... read more Acute Myocardial Infarction (MI) , 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 Ischemic Stroke ), or cardiac chambers. Thrombi can obstruct blood flow at the site of formation or detach and embolize to block a distant blood vessel (eg, 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 Pulmonary Embolism (PE) , embolic stroke).

Etiology of Thrombotic Disorders

Genetic defects that increase the propensity for venous thromboembolism include

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


Symptoms and Signs of Thrombotic Disorders

  • Chest pain and shortness of breath: Possible PE

  • Leg warmth, redness, and swelling: DVT

  • Weakness/numbness of one side of the body, problems speaking, and problems with balance and walking: Possible ischemic stroke

  • Abdominal pain: Possible mesenteric ischemia

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 noninduced embryonic or fetal death or passage of products of conception before 20 weeks gestation. Threatened abortion is vaginal bleeding without cervical dilation... read more .

Diagnosis of Thrombotic Disorders

Predisposing factors

Predisposing factors should always be considered. In some cases, the condition is clinically obvious (eg, recent surgery or trauma, prolonged immobilization, cancer, generalized atherosclerosis). If no predisposing factor is readily apparent, further evaluation should be conducted in patients with

  • Family history of venous thrombosis

  • More than one episode of venous thrombosis

  • Venous or arterial thrombosis before age 50

  • Unusual sites of venous thrombosis (eg, cavernous sinus, mesenteric veins)

As many as half of all patients with spontaneous DVT have a genetic predisposition.

Testing for predisposing congenital factors includes specific assays that measure the quantity or activity of natural anticoagulant molecules in plasma, and screening for specific gene defects, as follows:

  • Clotting assay for lupus anticoagulant

  • Clotting assay for resistance to activated protein C

  • Genetic test for factor V Leiden

  • Genetic test for prothrombin gene mutation (G20210A)

  • Functional assay of antithrombin

  • Functional assay of protein C

  • Functional assay of protein S

  • Antigenic assays of total and free protein S.

  • Measurement of plasma homocysteine levels

  • Immunoassays for antiphospholipid antibodies

Treatment of Thrombotic Disorders

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.

Treatment references

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Overview of Coagulation Disorders
Abnormal bleeding can result from disorders of the coagulation system, of platelets, or of blood vessels. Disorders of the coagulation system can be hereditary or acquired. Of the hereditary disorders of hemostasis, which of the following is the most common? 
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