CP19 Antithrombin III Deficiency


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CP19  Antithrombin III Deficiency



Antithrombin III (ATIII) deficiency may either be inherited or acquired.  Inherited ATIII deficiency follows an autosomal dominant transmission pattern.  A reduced amount of ATIII (usually below 50% of normal levels) constitutes the most common form.  Most often, patients presents between 15 and 30 years of age with lower limb thrombosis pulmonary embolism.  Other precipitating factors include pregnancy, surgery, and infection.

Acquired ATIII deficiency is more common than inherited deficiency.  Some causes of acquired ATIII deficiency are:

  1. Decreased synthesis of ATIII from liver cirrhosis
  2. Drug induced: L-Asparaginase, estrogens, heparin
  3. Increased excretion of ATIII : Protein losing enteropathy, nephritic syndrome, inflammatory bowel disease
  4. Accelerated consumption of ATIII: DIC, surgery
  5. Dilutional: cardiopulmonary bypass (CPB), autologous blood removal


Operative Management:

Antithrombin III deficiency in patients about to undergo CPB is largely a presumptive diagnosis based on substantial heparin resistance, e.g., failure to attain an ACT >400s after administration of 400U/kg of heparin.  Failure to recognize and correct heparin resistance are the onset of CPB is likely to produce low-grade activation of coagulation with consumption of platelets and procoagulants.  Although this can result in the formation of microemboli, a hemorrhagic diatheses is likely to follow the termination of CPB secondary to procoagulant consumption.


Cardiopulmonary Bypass

Are you certain the patient is really AT III deficient?

  1. Make sure the heparin was administered to the patient.
  2. IV line separation or loose connection?
  3. If administered peripherally, has the IV infiltrated?
  4. Check the heparin vial: has it expired or is the ot ineffective?
  5. Attempt to redoes the patient with 5,000 to 10,000U of a different biologic source of heparin, e.g. from porcine mucosal heparin to bovine lung.
  6. Once anesthesia has given 8-10 mg/kg of heparin, call the blood bank and order fresh frozen plasma (FFP).  Antithrombin III deficiench has been shown to respond to the administration of FFP, which contains normal concentrations of ATIII.  The volume of FFP needed to raise ATIII levels sufficiently to induce safe anticoagulation depends upon the magnitude of the deficiency, but 2-3U appears sufficient for most adults.


NOTE: Always alert the surgeon to the potentiality of an AT III deficiency, and confirm with anesthesia your proposed treatment plan.

  1. After the Administration of FFP, redose the patient with additional heparin.  Often, an additional 10,000U of heparin is sufficient to increase the ACT>480s
  2. Closely monitor your ACT values every 15 minutes.


Food for Thought

ACT prolongation after administration of FFP does not establish that  AT III deficiency caused the heparin resistance, because increasing plasma AT III levels should increase heparin-induced anticoagulation whether or not initial AT III levels are inadequate.  This may be important if the cause of heparin resistance is heparin-induced thrombocytopenia, or marked thrombocytosis.

In heparin-induced thrombocytopenia, an interaction of heparin, platelets, and immunoglobulin G (IgG) antibody is the likely mechanism for heparin resistance.  This would theoretically respond best to platelet-rich plasma pheresis accompanied by bolume replacement with FFP before CPB. After CPB and neutralization of heparin, platelet concentrates would be needed.  In marked thrombocytopenia, the treatment for heparin resistance would be the same, but the likely mechanism involved would be competitive heparin binding to platelets, inducing an acute release of platelet factor 4, and endogenous substance capable of binding and neutralizing heparin.

The use of FFP to replace ATIII may become obsolete with the recent introduction of a human ATIII concentrate, which has been used successfully to treat pregnancy induced AT III deficiency.

-Pooled from human plasma, but heat treated and should be free of infectious disease transmission risks.

-Half life of 22h.

-Capable of raising adult AT III levels by 30% with 1,000 U.

– Cost: approximately $1800 for 1,000 U.

-Use for heparin resistance in cardiac surgery has been reported.

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