HELP ! Lupus Anticoagulant & Measuring Heparinization for CPB

We are anticipating placing a patient on CPB for an AVR.

The patient has tested positive for Lupus Anticoagulant, so I looked up some things to assist in preparing for the case.

From what I have read, it seems the following points are salient regarding proper anticoagulant management during bypass.

  • ptt is going to be prolonged and unreliable
  • ACT will be prolonged and unreliable
  • AT III levels should be assayed and treated if abnormally low.
  • Empiric heparin dosing is suggested for CPB- most likely @ regimens higher than 300 units / kg
  • The HepCon is deemed effective for measurement of circulating heparin- but I am not taking that to the bank.

If anybody has experience with this sort of case- please contact me or preferably- leave a comment below this post in the comments section.

Any advice is sincerely appreciated.

Thank you very much-

Testing:

Lupus anticoagulant testing is used to help determine the cause of an unexplained thrombosis, recurrent miscarriages, or a prolonged PTT test. It is ordered to help determine whether a prolonged PTT is due to a specific inhibitor, such as an antibody against a specific coagulation factor or to a nonspecific inhibitor like the lupus anticoagulant. It may be ordered along with tests for cardiolipin antibody and anti-beta2-glycoprotein I to diagnose antiphospholipid syndrome. If someone has tested positive for the lupus anticoagulant, the series of tests may be done again in several weeks to see if the lupus anticoagulant is transient or persistent.

A sequence of several different tests is used to confirm the presence of a lupus anticoagulant. It is recommended that two tests be performed in order to detect lupus anticoagulant. The most sensitive tests are dilute Russell viper venom test (DRVVT) and a PTT or LA-sensitive PTT (PTT-LA), one that uses low levels of phospholipid reagents. Follow-up testing is performed to confirm or exclude the presence of lupus anticoagulant. These may include:

  • Mixing study: an equal volume of patient plasma is mixed with “normal” pooled plasma and a PTT or DRVVT is performed on this mixture.
  • Correction/neutralization: an excess of phospholipids is added to the patient sample and a PTT-LA or DRVVT is performed. (One such assay is called a hexagonal phase phospholipid assay).

A thrombin time test may also be done to rule out heparin contamination and a fibrinogen test may be done to rule out abnormal or deficient fibrinogen. These two conditions can cause prolongations in the test results and interfere with lupus anticoagulant detection.

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A Case Study:

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Lupus Anticoagulant and Off-pump Coronary Bypass: Dilemma of Anticoagulation

Madan M Maddali, MD, Maher J Albahrani, FCCP

Department of Anesthesia, Royal Hospital, Muscat, Sultanate of Oman

For reprint information contact: Madan M Maddali, MD Tel: 968 697 133 Fax: 968 697 133 Email: madan@omantel.net.om, Department of Anesthesia, Royal Hospital, PB No: 1331, PC: 111, Seeb, Muscat, Sultanate of Oman.

Discussion

“The hallmark of lupus anticoagulant is prolongation of the activated partial thromboplastin time. Our patient exhibited no systemic manifestation of lupus erythematosus, rheumatic, or other autoimmune diseases and probably had a primary antiphospholipid syndrome.

Circulating LA interferes with ACT values, and it is a challengefor the cardiac surgical team to monitor safe anticoagulationduring surgical procedures. Management of anticoagulation duringcardiopulmonary bypass for coronary bypass surgery and double-valvereplacement in patients with circulating antiphospholipid antibodieshas been documented.

However, we did not come across any reference to anticoagulation for OPCAB surgery in such patients.  We were faced with the problem of having to ensure adequate heparinization for a short duration of surgery when heparin assay, which has to be performed in the laboratory, takes longer than the duration of the surgical procedure.

Heparinization during OPCAB helps to maintain internal mammary artery patency after division of the distal end, and inhibits intravascular thrombin generation during coronary artery anastomosis.

This also provides anticoagulation backup in case of urgent conversion to on-pump surgery.

There are divergent opinionsregarding the appropriate dose of heparin for OPCAB, ranging from full heparinization to more modest doses. 

It is generally held that an ACT > 300 sec is adequate.

Our protocol specified 100 units·kg–1 that resulted in an ACT > 300sec.  We presumed that as regular heparin acts through AT III,the normal AT III level in our patient would ensure adequate anticoagulation.

If we could not have achieved an ACT > 300sec, we would probably have repeated the bolus of heparin. If the AT III level had been low, we would have considered ways to improve it, either by infusion of AT III concentrate or fresh frozen plasma.

The other option would have been to use another thrombin inhibitor such as lepirudin, argatroban, hirulog, ordesirudin, which were either not available or did not suit our immediate need.

Plasma tissue-type plasminogen activator and fibrin D-dimerlevels are higher in LA-positive patients who are prone to thrombosis.

We are unsure if the elevated postoperative fibrin D-dimer valuesin this case indicated a tendency for thrombosis.

The postoperativecardiac enzymes and electrocardiogram showed no signs of ischemia.However, anticoagulation was initiated with heparin at 6 hours postoperatively and was overlapped with warfarin on the 3rdpostoperative day.

Subsequently, heparin was withdrawn on the6th day and the patient was discharged home on warfarin.

It is important for clinicians to be aware that circulating LA may prolong aPTT.

We suggest that if AT III levels are normalin such patients, the anesthesiologists should follow the usual heparinization protocols to achieve safe anticoagulation levels.

However, in prolonged surgery, intra- and postoperative heparin assays may be needed to monitor anticoagulation and reversal.

It may be necessary to commence anticoagulation early in thepostoperative period to prevent thromboembolic episodes. Monitoringfibrin D-dimer levels may aid in the detection of subclinical thrombosis.”

Other Possibilities

“After heparin contamination, a lupus anticoagulant is the most common reason for a prolonged PTT.

Occasionally, testing may be ordered to help determine the cause of a positive VDRL/RPR test for syphilis as cardiolipin antibodies may produce a false positive result with these tests.

Patients on heparin or heparin substitute (such as hirudin, danaparoid, or argatroban) anticoagulation therapy may have false positive results for lupus anticoagulant, but those on warfarin (COUMADIN®) anticoagulant therapy should not. If possible, lupus anticoagulant testing should be done prior to the start of anticoagulation therapy. If someone with a thrombosis has a lupus anticoagulant, it may be necessary to prolong and possibly increase the intensity of their anticoagulation therapy.

In addition to testing for lupus anticoagulant, it may sometimes be necessary to test for coagulation factor VIII levels. Strong factor VIII inhibitors (specific antibodies against factor VIII) can decrease factor VIII levels and cause false positive lupus anticoagulant tests. Elevated factor VIII levels, as may be seen in an acute infection or with replacement therapy when someone has Hemophilia A, may shorten the PTT time, leading to a temporary false negative test for lupus anticoagulant.”

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