Interact CardioVasc Thorac Surg 2009;8:439-441. doi:10.1510/icvts.2008.193177
© 2009 European Association of Cardio-Thoracic Surgery
Proposal for bail-out procedures - Cardiac general |
Heparin-induced thrombocytopenia with thrombosis syndrome managed with plasmapheresis
Robert Kramera,*,
Payson Oberg-Higginsb,
Louis Russoa and
John H. Braxtona
a Division of Cardiothoracic Surgery, Maine Medical Center, 22 Bramhall St., Portland, ME 04102, USA
b Division of Nephrology, Maine Medical Center, 22 Bramhall St., Portland, ME 04102, USA
Received 2 September 2008;
received in revised form 12 December 2008;
accepted 15 December 2008
 Presented at the spring meeting of the Northern New England Cardiovascular Disease Study Group in Portland, Maine, USA, June 20, 2008.
*Corresponding author. Tel.: +1 207-662-2414; fax: +1 207-662-6038.
E-mail address: kramer{at}mmc.org (R. Kramer).
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Abstract
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Heparin-induced thrombocytopenia with thrombosis syndrome is an antibody-mediated disorder that has a high mortality in cardiac surgical patients in spite of early diagnosis and management with direct thrombin inhibitors. Plasmapheresis, an extracorporeal technique that has been designed for the removal of large molecular weight substances from the plasma, can remove the offending antibodies from these desperately ill patients. We describe a case of a postoperative cardiac surgery patient with heparin-induced thrombocytopenia with thrombosis syndrome and multi-system failure who was dependent upon a left ventricular assist device. He was treated successfully with plasmapheresis with recovery of his platelet count from 25,000/µl to over 200,000/µl, along with multi-organ recovery. This patient survived because of plasmapheresis. Removing the antibodies to the heparin-platelet factor four complex with plasmapheresis is an effective strategy to treat these patients. We believe that the use of plasmapheresis as a bail-out procedure in these often desperately ill post-operative cardiac surgical patients who have heparin-induced thrombocytopenia with thrombosis syndrome could be lifesaving.
Key Words: Thrombosis; Blood platelets; Immunochemistry; Hematology
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1. Introduction
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Heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) can be a disastrous complication of cardiac surgery. HITTS is caused by antibodies to the heparin-platelet factor four complex (H-PF4), making heparin a pro-coagulant. We make the diagnosis of heparin-induced thrombocytopenia (HIT) or HITTS based on a scoring system (Table 1) adapted from Warkentin et al. [1, 2]. The scoring algorithm incorporates thrombocytopenia, timing, evidence of thrombosis, and the potential for other causes of thrombocytopenia. We have been frustrated by the high mortality in this group of patients in spite of placing most post-operative cardiac surgical patients in a heparin-free environment and early administration of direct thrombin inhibitors to patients with HIT.
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Table 1 Scoring system (adapted from Warkentin) used as an aid in making the clinical diagnosis of heparin-induced thrombocytopenia and heparin-induced thrombocytopenia with thrombosis syndrome
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Plasmapheresis, or therapeutic plasma exchange, is an extracorporeal technique that has been designed for the removal of large molecular weight substances from the plasma. Autoantibodies, immune complexes, cryoglobulins, and cholesterol containing lipoproteins are examples of such substances. Most of the plasmapheresis done in the United States is for neurologic, immunologic, or hematologic diseases [3]. Plasmapheresis has also been found to be effective in HITTS by removing the pathogenic immunoglobulins [4–7].
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2. Material and methods
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In an effort to decrease the high mortality of HITTS, we have initiated a trial of plasmapheresis that was approved by our local Institutional Review Board on November 27, 2007. In order to be considered for this protocol, the patient must have a HITTS score in the moderate or high range according to our scoring system with clinical evidence of thrombosis.
During plasmapheresis, the patient's plasma is replaced by fresh frozen plasma and/or albumin. Because clotting factors and antibodies other than those to H-PF4 are removed during plasmapheresis, patients with the following are excluded from our protocol: (1) obvious severe bleeding (e.g. gastrointestinal, surgical), (2) major hemoglobin drop within 48 h of HITTS diagnosis, (3) intracerebral bleeding, (4) known immunoglobulin G deficiency, (5) sepsis with positive blood cultures, and (6) hepatic failure.
A 60-year-old white male with a history of hypothyroidism and no recent history of heparin exposure presented at an outside hospital having suffered an acute anterolateral myocardial infarction while exercising. After receiving thrombolytic therapy, he was transferred to our center in cardiogenic shock.
Upon arrival, he was transferred emergently to the cardiac catheterization laboratory where he remained in shock, developed respiratory failure, and had a cardiac arrest. He was found to have severe left ventricular hypokinesis with an ejection fraction of 20% and three-vessel coronary artery disease with a thrombus of the left main coronary artery. An intra-aortic balloon pump (IABP) was placed.
The patient was transferred directly to the operating room and underwent triple coronary artery bypass grafting and was unable to be separated from cardiopulmonary bypass. An extracorporeal membrane oxygenator (ECMO) was placed and he was transferred to the intensive care unit. On the second postoperative day, he was returned to the operating room for placement of a HeartMate® (Thoratec Corporation, Pleasanton, CA, USA) left ventricular assist device (LVAD) and an ECMO right ventricular device (RVAD). He was separated from the ECMO RVAD two days later.
The patient received unfractionated porcine-derived heparin during the first 10 days of his hospitalization with thrombocytopenia being documented within the first 24 h. At first, the thrombocytopenia was thought to be related to causes other than HIT. By the 10th postoperative day his toes became cyanotic, heparin was eliminated from his regimen, and a direct thrombin inhibitor, bivalirudin, was initiated. Enzyme Linked ImmunoSorbent Assay (ELISA) to detect antibodies to H-PF4 was negative. The likelihood of HITTS according to the scoring system noted above was in the moderate range. By the 12th postoperative day, all toes were necrotic, the platelet count remained in the range of 25,000/µl, the patient was comatose, had respiratory failure, renal failure and evidence of hepatocellular dysfunction. He required mechanical ventilation and continuous renal replacement therapy with Prisma® (Gambro Corporation, Lakewood, CO, USA).
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3. Results
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Plasmapheresis was initiated after obtaining informed consent from the patient's wife. After the first plasmapheresis, the platelet count climbed from 25,000/µl to 38,000/µl. According to our protocol, plasmapheresis was done every other day for a total of five exchanges, using fresh frozen plasma and albumin to replace the plasma removed. After the third exchange, platelets had risen to over 200,000/µl and the patient had improved in all respects. He awakened with full cognition along with reversal of his multi-system failure. Subsequently, amputations were performed (transmetatarsal on one side, and all toes on the other). Renal function improved to near normal, bivalirudin was transitioned to warfarin, and the patient was eventually discharged to his home with the HeartMate® LVAD awaiting cardiac transplantation.
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4. Discussion
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In cardiac surgery, ELISA is positive in up to 12% of pre-operative patients and in 27–50% of postoperative patients, [1, 2] not all of whom have HIT or HITTS. At times, we have found that in some high scoring patients, ELISA may not be positive until three or four determinations have been made, emphasizing the need to make the diagnosis clinically. Amiral et al. [8] found that although most of the autoantibodies are directed toward H-PF4 in HITTS, there were patients with HITTS who showed no detectable anti-H-PF4 antibodies. Amiral's group hypothesized an alternative mechanism. It is our practice to use ELISA as a confirmatory test and not to rely on its negativity.
In spite of reports describing the use of plasmapheresis for HITTS there has not been widespread adoption of this strategy in the management of this syndrome. We are convinced that the patient in this case report did have HITTS and that he survived because of plasmapheresis. This case report emphasizes the importance of plasmapheresis as a lifesaving strategy and its value as a bail-out procedure in the management of patients with HITTS.
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Acknowledgements
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The authors thank Robert Groom and Ken Cournoyer from the Division of Perfusion for Heartmate® support and Robert Groom, Paul Weldner, Sonia Kamath and Norma Albrecht for manuscript review.
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References
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- Warkentin TE. Heparin-induced thrombocytopenia; pathogenesis and management. Br J Haematol 2003;121:535–555.[CrossRef][Medline]
- Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 2003;76:638–648.[Abstract/Free Full Text]
- Linenberger ML, Price TH. Use of cellular and plasma apheresis in the critically ill patient: part II: clinical indications and applications. J Intensive Care Med 2005;20:88–103.[Abstract/Free Full Text]
- Robinson JA, Lewis BE. Plasmapheresis in the management of heparin-induced thrombocytopenia. Semin Hematol 1999;36(Suppl_1):29–32.[Medline]
- Antonijevic NM, Savic NB, Perunicic J, Kovac M, Mikovic D, Stanojevic M, Calija B, Milosevic RA, Obradovic SD, Vasiljevic Z. Salvage late plasmapheresis in a patient with pulmonary embolism caused by heparin-induced thrombocytopenia resistant to danaparoid sodium and lepirudin. J Clin Apheresis 2006;21:252–255.[CrossRef][Medline]
- Poullin P, Pietri PE, LefÈvre P. Heparin-induced thrombocytopenia with thrombosis: successful treatment with plasma exchange. Br J Haematol 1998;102:629–630.[Medline]
- Vender JS, Matthew EB, Silverman IM, Konowitz H, Dau PC. Heparin-associated thrombocytopenia: alternative managements. Anesth Analg 1986;65:520–522.[Abstract/Free Full Text]
- Amiral J, Marfaing-Koka A, Wolf M, Alessi MC, Tardy B, Boyer-Neumann C, Vissac AM, Fressinaud E, Poncz M, Meyer D. Presence of autoantibodies for interleukin-8 or neutrophil activating peptide-2 in patients with heparin-associated thrombocytopenia. Blood 1996;88:410–416.[Abstract/Free Full Text]
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Abstract
1. Introduction
