HIT and heparin alternatives

Took care of a patient who came to OR for a redo-sternotomy and triple valve replacement on ECMO.

Scroll down to see how we managed the patient’s possible HIT.  The patient had a low score on her 4Ts assessment.  Therefore, we opted to move forward before the functional assay came back with results as the patient was in dire need of triple valve replacement.

 


HIT Basics

Heparin Induced Thrombocytopenia and Cardiac Surgery: A Comprehensive Review. J Blood Disord Transfus 2011, S2.

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From https://www.omicsonline.org/open-access/heparin-induced-thrombocytopenia-and-cardiac-surgery-a-comprehensive-review-2155-9864-S2-003.pdf

The goals of treatment for HIT are threefold: Interrupt the pathological immune response, inhibit the uncontrolled generation of thrombin, and minimize the complications.

Cessation of heparin alone does not sufficiently reduce the risk of thrombosis. The next step in management targets the uncontrolled generation of thrombin with the use of direct thrombin inhibitors (DTIs).  Argatroban is preferred in patients with renal insufficiency, whereas lepirudin is the drug of choice for patients with liver disease.  Bivalirudin is another hirudin analog that differs from lepirudin in that it is hemodialyzable and primarily undergoes enzymatic elimination. Its half-life is the shortest, 20-25 minutes, making bivalirudin the safest option since there are no reversal agents available.

All three agents can be monitored using the activated partial thromboplastin time (aPTT) to levels of 1.5 to 2.0 above baseline. Once the platelet count has increased to a minimum of 150,000/µL bridging therapy to warfarin is essential for the safe transition from DTIs.

Iloprost is a prostacyclin analogue that reversibly inhibits platelet aggregation.  Plasma exchange was successful in reducing anti-P4/heparin antibodies and allowed for the restoration of a normal platelet count, essentially reversing the disease.

A-suggested-approach-to-diagnosis-and-initial-management-of-patients-with-suspected-HIT
From https://www.researchgate.net/figure/A-suggested-approach-to-diagnosis-and-initial-management-of-patients-with-suspected-HIT_fig1_236255402

HIT/HITT and alternative anticoagulation: current concepts. BJA: British Journal of Anaesthesia, Volume 90, Issue 5, 1 May 2003, Pages 676–685.

Heparin-induced thrombocytopenia and cardiac surgery. Curr Opin Anaesthesiol, 2010; 23:74–79.

Perioperative care in cardiac anesthesia and surgery.  Chapter 19: HIT and heparin alternatives.  

Handbook of patient care in cardiac surgery. Chapter 2: Operative management.


Prostacyclins in Cardiac Surgery: Coming of Age.  Seminars in Cardiothoracic and Vascular Anesthesia 22(3):108925321774929 · December 2017.

Intraoperative infusion of epoprostenol sodium for patients with heparin-induced thrombocytopenia undergoing cardiac surgery. The Japanese Journal of Thoracic and Cardiovascular Surgery. Volume 54, Issue 8, pp 348–350.

Cardiac Surgery With Cardiopulmonary Bypass in Patients With Type II Heparin-Induced Thrombocytopenia. Ann Thorac Surg 2001;71:678–83.

HIT and urgent open heart surgery: a sticky situation. Grand Rounds, Hematology. UW 2015. 


Screen Shot 2018-12-19 at 8.45.41 PM
From https://www.omicsonline.org/open-access/percutaneous-coronary-intervention-in-patients-with-heparin-inducedthrombocytopenia-case-report-and-review-of-literature-2329-6607-1000202.php?aid=82752

Bivalirudin for Cardiopulmonary Bypass in the Setting of Heparin-Induced Thrombocytopenia and Combined Heart and Kidney Transplantation— Diagnostic and Therapeutic Challenges. Journal of Cardiothoracic and Vascular Anesthesia 31 (2017) 354–364.

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From https://www.jcvaonline.com/article/S1053-0770(16)30273-7/fulltext

Cardiac Bypass Surgery in the Setting of Heparin Induced Thrombocytopenia.  BIDMC guidelines.

Anticoagulation during Cardiopulmonary Bypass in Patients with Heparin-induced Thrombocytopenia Type II and Renal Impairment Using Heparin and the Platelet Glycoprotein IIb–IIIa Antagonist Tirofiban. Anesthesiology 2 2001, Vol.94, 245-251. 

Management of anticoagulation in patients with subacute heparin-induced thrombocytopenia scheduled for heart transplantation. BLOOD, 15 NOVEMBER 2008 VOLUME 112, NUMBER 10; 4024-4027.

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From http://www.bloodjournal.org/content/bloodjournal/112/10/4024.full.pdf?sso-checked=true

 

What we did:

  • Prior to giving heparin, we started alprostadil (PGE1) infusion at 1mcg/min and increased the doseage as tolerated to 5mcg/min.  We did offset the hypotension with levophed and vasopressin.
  • We gave our routine dose of heparin.
  • No heparin resistance noted.  Because this would be a long pump run, we opted to give an antifibrinolytic infusion as well as bolus.
  • This patient required higher than normal amounts of pressors and ultimately received methylene blue to help with vasoplegia.
  • We reversed the heparin with protamine and stopped the PGE1 at that time.

Antithrombin III

The other day we had a patient come in for a CABG. Aside for some coronary artery disease, hypertension, and chronic kidney disease, the patient was pretty healthy. They were not on anticoagulation prior to the procedure.

After I gave full dose heparin for going on bypass (41,000U in this case), the ACT only came up to 422. An additional 10,000U of heparin was given with a repeat ACT of 457. Still, our surgeon was not quite comfortable with that number and requested an additional 10,000U heparin. The ACT came to 477.

If the ACT stayed in the low 400s, would you go on bypass? What if the ACT had not responded to the repeated heparin dosings?

Management of coagulation during cardiopulmonary bypass. Continuing Education in Anaesthesia Critical Care & Pain, Volume 7, Issue 6, 1 December 2007, Pages 195–198, https://doi.org/10.1093/bjaceaccp/mkm036.

Antithrombin III concentrate to treat heparin resistance in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2002 Feb;123(2):213-7.

Would you give antithrombin III or plasma?

Treating Heparin Resistance With Antithrombin or Fresh Frozen Plasma. The Annals of Thoracic Surgery. June 2008Volume 85, Issue 6, Pages 2153–2160.

Is there evidence that fresh frozen plasma is superior to antithrombin administration to treat heparin resistance in cardiac surgery? Interact Cardiovasc Thorac Surg. 2014 Jan; 18(1): 117–120.

We ultimately decided to go on bypass. Repeat ACTs on bypass were in the 500s. No antithrombin was given. After separation from cardiopulmonary bypass and administration of protamine, repeat ACT was 111. Protamine was dosed accordingly to heparin administration and ACTs while on bypass.

Recommendations for the use of antithrombin concentrates and prothrombin complex concentrates. Blood Transfus. 2009 Oct; 7(4): 325–334.

Thrombate (antithrombin III) package insert