Activated protein C resistance (APCR)
Protein C Anticoagulant Pathway: Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. Activated protein C (APC) functions as a circulating anticoagulant, which specifically degrades and inactivates the phospholipid-bound factors Va and VIIIa. This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S
Specialty	Hematology

Activated protein C resistance (APCR) is ahypercoagulability (an increased tendency of the blood to clot) characterized by a lack of a response to activatedprotein C (APC), which normally helps prevent blood from clotting excessively. This results in an increased risk ofvenous thrombosis (blood clots in veins), which resulting in medical conditions such asdeep vein thrombosis (usually in the leg) andpulmonary embolism (in the lung, which can cause death).^[1] The most common cause of hereditary APC resistance isfactor V Leiden mutation.

An estimated 64 percent of patients withvenous thromboembolism may have APC resistance.^{[2][needs update]}

The disorder can be acquired or inherited, the hereditary form having anautosomaldominant inheritance pattern.^[3]

APC (with protein S as a cofactor) degradesFactor Va andFactor VIIIa. APC resistance is the inability of protein C to cleaveFactor Va and/orFactor VIIIa, which allows for longer duration ofthrombin generation and may lead to a hypercoagulable state. This may be hereditary or acquired.^[4] The best known and most common hereditary form isFactor V Leiden, which is responsible for more than 95% of cases.^[5] Other genetic causes include Factor V Cambridge (VThr306) and the factor V HR2 haplotype (A4070G mutation).^[5][6] Acquired forms of APC resistance occur in the presence of elevated Factor VIII concentrations.^{[citation needed]}Antiphospholipid antibodies,^[5]pregnancy, and certain forms ofestrogen therapy, such asethinylestradiol-containingbirth control pills, have been found to produce acquired APC resistance.^{[7][8][9][10][11][12][13][14][excessive citations]}

APC resistance can be evaluated using anAPC resistance test.^[15] There are two types of APC resistance tests with different properties: theactivated partial thromboplastin (aPTT)-based test and theendogenous thrombin potential (ETP)-based test.^{[9][10][11][16]}

Asymptomatic individuals with APC resistance (e.g.,heterozygousfactor V Leiden) are not normally treated unless additionalrisk factors forthrombosis are also present.^[17] An example issurgery, in which perioperative short-termanticoagulation may be used.^[17] However, people withhomozygous factor V Leiden, and people with heterozygous factor V Leiden who have an additionalthrombophilic condition (e.g.,antithrombin deficiency,protein C deficiency, orprotein S deficiency), should be considered for lifelongoral anticoagulation therapy.^[17] People with APC resistance and initial DVT are treated with a standard anticoagulant regimen, for instanceintravenousheparin therapy followed by oral anticoagulation.^[17]

• Coagulopathies
• Defects of enzyme cofactors

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