How are coagulation-promoting nonplatelet hemostatic disorders diagnosed?

Updated: Oct 28, 2019
  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
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Answer

Answer

Deficiencies of antithrombin III, protein C, and protein S are defined as an absence or a reduced level of protein leading to an increased risk for thrombosis. These deficiencies can be congenital or acquired. [54] The former are caused by partial or complete gene deletions, replacements, and rearrangements. [55]

Antithrombin III deficiencies take several forms and may be quantitative or qualitative. The following have been described [56] :

  • Loss of the entire molecule
  • Diminution of activity only, with normal concentration
  • Normal activity and concentration but with a decreased sensitivity to heparin
  • Diminished production of antithrombin III
  • Increased loss of antithrombin III
  • Increased consumption of the inhibitor

Antithrombin III deficiency should be considered in any patient who cannot be adequately anticoagulated on heparin or who develops thrombosis while on heparin in the absence of heparin-induced thrombocytopenia. FFP or highly purified concentrates should be administered before starting heparin for patients needing anticoagulation. Adequate antithrombin substitution is lifesaving in patients whose cases of DIC are caused by septic or traumatic shock. Protein C and S deficiencies follow a similar pattern and have similar clinical manifestations.

Factor V has both procoagulant and anticoagulant properties. Activated factor V stimulates the formation of thrombin, whereas anticoagulant factor V acts as a cofactor for aPC in the degradation of factor VIII and factor VIIIa, thereby reducing thrombin formation. High procoagulant factor V levels may enhance prothrombinase activity and increase the risk of thrombosis. Factor V with the Leiden mutation is resistant to aPC lysis compared with the wild type. Resistance to aPC is the most common inherited hypercoagulable state associated with venous thrombosis.

Low anticoagulant factor V levels can reduce aPC cofactor activity in the inactivation of factor VIII (aPCR phenotype), which might also promote thrombosis. Low factor V levels in combination with factor V Leiden could lead to a more severe aPCR phenotype (pseudohomozygous aPCR). [57]


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