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Ann Thorac Surg 1996;61:920-924
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Cardiopulmonary Bypass in Patients With Heparin-Induced Thrombocytopenia Using Org 10172

Departments of Thoracic and Cardiovascular Surgery, Pediatric Cardiology, Anesthesiology, and Internal Medicine, University of Münster, Münster, Germany

Accepted for publication November 24, 1995.

	Abstract

Top Footnotes Abstract Introduction Case Reports Comment References

 
Background. In patients with heparin-induced thrombocytopenia undergoing cardiac operations, anticoagulation with heparin should be avoided. The low-molecular-weight glycosaminoglycan Orgaran has been used as an alternative, but the overall experience is limited.

Methods. Two patients with heparin-induced thrombocytopenia underwent cardiopulmonary bypass using Orgaran for anticoagulation. A 30-year-old woman suffered from emboli to her brain through a secondary atrial septal defect, a 14-year-old boy from ischemia of his left leg due to recurrent embolism originating from the mitral valve. In both cases, cardiopulmonary bypass was performed in a routine manner, except for using low-dose Orgaran instead of heparin. Anticoagulation was monitored during cardiopulmonary bypass by measuring Orgaran plasma levels and activated clotting time.

Results. No thromboembolic or bleeding complications occurred during and after atrial septal defect repair and mitral valve replacement, respectively. In the former case, thrombotic material from the inferior vena cava was removed during hypothermic circulatory arrest within the same procedure. Activated clotting time did not correlate with plasma levels of Orgaran.

Conclusions. Orgaran might be a useful alternative for anticoagulation during extracorporeal circulation. Adequate dosages and measurement of plasma levels are recommended for its use in cardiopulmonary bypass.

	Introduction

Top Footnotes Abstract Introduction Case Reports Comment References

 
Heparin is commonly used for anticoagulation in cardiopulmonary bypass procedures. Several side effects of heparin such as hypersensitivity reactions, hypereosinophilia, and severe osteopenia are well known [1, 2]. Its most dangerous adverse effect, however, is the so-called type II heparin-induced thrombocytopenia (HIT). It occurs in up to 3% of all heparin-treated patients [3]. Heparin-induced thrombocytopenia is often accompanied by arterial and venous thrombosis, resulting in considerable morbidity and mortality. The overall risk for limb amputation is about 20%, and the mortality rate is up to 30% [4]. Orgaran (Org 10172; N. V. Organon, BH Oss, Netherlands), a natural low-molecular-weight glycosaminoglycan consisting of a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate, has been shown to have a much lower cross-reactivity (about 10%) with heparin-induced antibodies compared with low-molecular-weight heparins (>90%) [5]. The efficacy of Orgaran for anticoagulation during cardiopulmonary bypass was first shown in animals and later also in humans with HIT [5–7]. We report on 2 patients with HIT who underwent operation for closure of a secondary atrial septal defect and mitral valve replacement, respectively, using Orgaran for anticoagulation during cardiopulmonary bypass. One of them was a 30-year-old woman who was exposed to deep hypothermia with circulatory arrest, and the other a 14-year-old boy. With this report we want to present our experience with Orgaran as a substitute for heparin in cardiopulmonary bypass and provide some practical information for its use.

	Case Reports

Top Footnotes Abstract Introduction Case Reports Comment References

 
Patient 1
A 30-year-old woman presented with a 7-year history of neurologic symptoms. After a cesarean section for preeclamptic syndrome in July 1988 she suffered from headaches located behind her left eye, which were thought to be related to an amotio retinae. The electroencephalogram, however, revealed a left-sided focus; a computed tomographic scan was normal. The patient was treated with subcutaneous heparin (3 x 5,000 U/day) for 1 week. A control electroencephalogram 3 months later did not show the former focus any more. In February 1989, the patient was admitted to the Department of Neurology with a hyperkinetic syndrome and dysarthria. A somatic cause could not be visualized at that time; computed tomographic scan and electroencephalography as well as studies on cerebrospinal fluid were normal. In October 1993, during the 19th week of her fourth pregnancy, the patient had a generalized seizure, and 4 weeks later she suffered from Broca's dysphasia combined with a right-sided hemiparesis and a homonymous hemianopia to the right side. Diagnostic procedures including magnetic resonance imaging and transcranial Doppler ultrasonography now showed multiple cerebral embolic insults within the areas of the left medial and posterior cerebral artery. Echocardiography suggested an atrial septal aneurysm as the most likely cause of the cerebral emboli; intracardiac thrombi or a right-to-left shunt could not be detected. However, during a Valsalva procedure transcranial ultrasonography demonstrated multiple emboli within the left medial cerebral artery. A deep vein thrombosis was not evident. To prevent further embolization anticoagulation was started with intravenous heparin (25,000 to 30,000 U/day). Within a few days, platelet counts dropped from normal values to 70,000/µL. Heparin-induced thrombocytopenia was diagnosed by a heparin-induced platelet activation assay, showing platelet aggregation in the presence of heparin. Heparin administration was discontinued, and Orgaran treatment was initiated. Until delivery of a healthy baby in January 1994, Orgaran plasma levels were kept in a range of 0.4 to 0.8 U/mL using an anti-Xa assay (Berichrom Heparin; Behringwerke, Marburg, Germany). Thereafter, anticoagulation was changed to an oral medication. The neurologic symptoms resolved, and no other embolic event occurred.

In January 1995, the patient was admitted to our institution for resection of the suspected atrial septal aneurysm. Oral anticoagulation was discontinued, and Orgaran treatment resumed. Orgaran was adjusted to a plasma level of 0.4 to 0.8 U/mL (3,000 U/day) corresponding to an activated clotting time (ACT) of 175 seconds. A standard roller pump (Stöckert, Munich, Germany) and a membrane oxygenator (Univox; Baxter Healthcare Corporation, Bentley Division, Irvine, CA) were used for cardiopulmonary bypass. The priming consisted of two units of packed red blood cells added to Ringer's solution (1,600 mL), aprotinin (2,000,000 U), and human albumin (250 mL). Before institution of cardiopulmonary bypass the patient received a bolus of 5,250 U of Orgaran, resulting in a peak level of 1.087 U/mL and an ACT of 298 seconds. During operation a secondary atrial septal defect covered by a Chiari net was found. A septal aneurysm was not evident. The atrial septal defect was directly closed and the Chiari net resected. Subsequently, the patient was cooled down to 22°C and circulatory arrest initiated to explore the inferior vena cava. Masses of thrombotic material were removed from the inferior vena cava. At the end of cardiopulmonary bypass, 300 mg of protamine sulfate was given. At the first postoperative day, a continuous infusion of Orgaran (90 U/h) was started to keep the Orgaran plasma level at 0.4 to 0.8 U/mL. As the prothrombin time was within therapeutic limits at the end of the first postoperative day, Orgaran treatment was discontinued and oral anticoagulation started again. Total postoperative drainage was 440 mL. Three units of packed red blood cells and five units of fresh frozen plasma were given postoperatively. Transfusion of platelets or clotting factors was not necessary. At all times preoperatively, intraoperatively, and postoperatively, platelet counts exceeded 100,000/µL. On the fourth postoperative day the patient was discharged and referred to her county hospital, where she experienced an uneventful recovery.

Patient 2
A 14-year-old boy who had been complaining of claudication-like pain in his left leg for several weeks was admitted to the emergency room with a pale and painful left leg after a soccer match. The pulses of the left popliteal, the posterior tibial, and the dorsalis pedis arteries were not palpable and not detectable by Doppler ultrasound. Angiography of the left femoral artery showed multiple emboli at the femoral bifurcation, and emergency embolectomy of the left femoral artery was performed. The histologic examination revealed an organized thrombus. Transthoracic and transesophageal echocardiography showed multiple 3-mm to 5-mm tumors attached to the chordae tendineae of the mitral valve. The mitral valve itself as well as the remaining heart valves appeared normal. Left atrium and ventricle were free of thrombi. An atrial septal defect as cause for paradoxical emboli could be ruled out. Subsequently, intravenous administration of heparin was started. A few days later, the patient suffered from amaurosis fugax despite effective anticoagulation, and platelet counts dropped to 60,000/µL. The diagnosis of type II HIT was confirmed by the heparin-induced platelet activation assay. Heparin administration was discontinued and Orgaran administration begun. Cardiac operation for resection of the tumors was urgently scheduled.

As in the first case, a roller pump (Stöckert) and a membrane oxygenator (Univox) were used for extracorporeal circulation with a similar priming. Before extracorporeal circulation, a bolus of 5,000 U of Orgaran was given resulting in drug levels greater than 1.5 U/mL during cardiopulmonary bypass and an ACT of 200 seconds. The patient was cooled down to 28°C during extracorporeal circulation. Intraoperatively, multiple white, solid, pea-like tumors were found attached to the chordeae tendineae of the posterior papillary muscle and posterior leaflet of the mitral valve (Fig 1). Complete removal of the multiple tumors required resection of the posterior leaflet and papillary muscles involved. A mechanical mitral valve prosthesis (21 mm; St. Jude Medical, St. Paul, MN) was implanted, preserving the anterior leaflet. After termination of extracorporeal circulation ACT was 132 seconds. During the postoperative period, Orgaran levels were adjusted to 0.4 to 0.8 U/mL. Total postoperative drainage was 700 mL. Two units of packed red blood cells, one unit of fresh frozen plasma, and two units of platelets were transfused postoperatively. Clotting factors were not given. Platelet counts increased from 66,000/µL on the first postoperative day to more than 100,000/µL on the second postoperative day. Oral anticoagulation was resumed 2 days later.

View larger version (81K): [in this window] [in a new window]   Fig 1. . Posterior papillary muscle and posterior leaflet of the mitral valve with multiple white, solid, pea-like tumors intraoperatively resected in patient 2.

	Comment

Top Footnotes Abstract Introduction Case Reports Comment References

 
Heparin-induced thrombocytopenia is commonly divided into two subtypes. Type I is characterized by an early onset and only a mild decrease (usually not less than 100,000/µL) in platelet count. The patients remain asymptomatic. The pathologic mechanism is presumably related to the platelet proaggregatory effect of heparin itself [8]. In contrast, in type II HIT, the onset is delayed and thrombocytopenia more severe. Platelet counts drop to less than 100,000/µL or less than 50% of baseline after 6 or more days of heparin treatment. Patients with HIT type II are at high risk for arterial or venous thrombosis with fatal outcome [9]. Type II HIT is thought to be mediated by immunologic mechanisms. Heparin and platelet factor-4 form multimolecular complexes representing a major antigen. These multimolecular complexes probably bind to HIT antibodies and consecutively activate platelets by binding to platelet FC receptors [10]. The immune complexes may also form on the surface of endothelial cells containing endogenous heparin, thus resulting in activation of these cells [11]. This simultaneous activation of platelets and endothelial cells may be responsible for the unique clinical presentation of type II HIT with formation of arterial and venous thrombosis [10].

Usually, the diagnosis of HIT is suspected after a significant decrease of platelet counts following heparin treatment. In our patients, we confirmed diagnosis by a heparin-induced platelet activation assay, which was positive in both patients [9]. This heparin-induced platelet activation test is more sensitive compared with the previously used platelet aggregation assay and is superior to the carbon-14–serotonin release assay due to its ability to differentiate the cross-reactivity with different types of heparin, low-molecular-weight heparins, and heparinoids such as Orgaran [9, 12].

Treatment of HIT consists of immediate discontinuation of heparin administration and initiation of alternative anticoagulation, if necessary. Many different drugs have been evaluated as a substitute for heparin. Sodium warfarin is very effective but usually not suitable as it takes about 2 to 3 days until a therapeutic range is reached. Antiplatelet drugs, such as acetylsalicylic acid or dipyridamole, have not been proved safe enough to provide effective anticoagulation in high-risk situations like cardiopulmonary bypass procedures. Prostacyclin analogues such as iloprost, which are supposed to reversibly inhibit platelet aggregation, may permit safe heparin administration for cardiovascular operations [13]. Ancrod, a rapid-acting defibrinogenating agent derived from the Malayan pit viper, has been used for anticoagulation in deep venous thrombosis and pulmonary embolism as well as for cardiopulmonary bypass [14, 15]. Due to its structural difference from heparin, ancrod does not cause immune-mediated thrombocytopenia, but excessive bleeding and secondary sensitization may occur [5, 14], and routine use for cardiopulmonary bypass cannot be recommended yet. Recently, thrombin inhibitors were suggested as a substitute for heparin in HIT [16], and experimental studies with cardiopulmonary bypass have already been performed in animals [17]. However, their applicability for cardiopulmonary bypass in humans is unclear at this time. Successful treatment of HIT has also been reported with application of immunoglobulins and with administration of intravenous streptokinase or plasmapheresis [18, 19], but these therapeutic options do not seem suitable for cardiopulmonary bypass procedures.

In 1984, low-molecular-weight heparins were introduced as treatment of HIT [20]. Massonnet-Castel and associates [21] successfully used low-molecular-weight heparins for anticoagulation during cardiopulmonary bypass. However, Horellou and colleagues [22] reported on persistent thrombocytopenia in patients receiving low-molecular-weight heparins. These different findings may be explained by the reported high cross-reactivity rate of heparin-dependent antibodies of up to more than 90% and the capability of inducing platelet aggregation [5, 23]. Orgaran, however, has been shown to have a low cross-reactivity rate (10% to 18%) [5]. In a clinical trial including 230 patients with HIT, Orgaran has been well tolerated even in high dosages. Orgaran treatment was successful in 92.8% of all patients, thereby reducing the mortality rate related to thromboembolic complications from 30% to 5.1%. However, lethal bleeding, thrombosis, and septic shock may be caused by Orgaran in about 3.0% [5]. Therefore, patients should undergo laboratory tests to exclude an unfavorable cross-reactivity. Orgaran is eliminated by the kidneys and is not metabolized in the liver. The half-life of plasma anti-Xa activity is 25 hours, and 7 hours for inhibition of thrombin formation. Care should be taken in patients with reduced liver and kidney function and in patients with bronchial asthma. Its first successful use during cardiopulmonary bypass procedures was reported recently [5, 7]. Despite the scarce knowledge about the drug we decided to treat our patients with Orgaran during extracorporeal circulation as alternative treatment modalities were not available.

Orgaran was given as a single bolus before extracorporeal circulation. Measurement of ACT did not provide useful information as it showed only a mild increase in 1 case and even a decrease in the other. Although in neither case the otherwise recommended prolongation [7] of ACT could be achieved, anticoagulation seemed to be effective, because during extracorporeal circulation and hypothermic circulatory arrest no thromboembolic events occurred and no clot formation could be observed in the heart-lung machine. Our data are very limited, but they suggest that ACT measurement is not reliable for monitoring anticoagulation during cardiopulmonary bypass. In our opinion, the previously demonstrated flat dose–response relationship between the applied dose of Orgaran and the standard clotting assays like partial thrombin time or ACT makes direct monitoring of anti-Xa activity necessary [24]. The measurement of plasma Orgaran levels can be easily done by a standardized and validated assay [25]. During cardiopulmonary bypass we kept the Orgaran levels between 1.0 and 1.5 U/mL, and lowered them to 0.4 to 0.8 U/mL after operation, corresponding to an infusion rate of 0.01 to 0.02 U•kg^-1•min^-1 (Figs 2, 3). Partial thrombin time was normal at this time. Monitoring of Orgaran plasma levels during cardiac operation is recommended by the manufacturer at 10 minutes after the initial bolus and 10 minutes after institution of cardiopulmonary bypass as well as once or twice during the operation.

View larger version (15K): [in this window] [in a new window]   Fig 2. . Course of activated clotting time (ACT) and Orgaran plasma levels in patient 1 before, during, and after extracorporeal circulation (ECC). (POD = postoperative day.)

View larger version (15K): [in this window] [in a new window]   Fig 3. . Course of activated clotting time (ACT) and Orgaran plasma levels in patient 2 before, during, and after extracorporeal circulation (ECC). (POD = postoperative day.)

In conclusion, Orgaran might be a useful alternative to heparin during extracorporeal circulation in patients with type II HIT. Pediatric cardiac operations and high-risk procedures such as hypothermic circulatory arrest may not be excluded from its use. Adequate dosages can reduce bleeding complications and the need for use of blood products. Measurement of Orgaran plasma levels is recommended for monitoring of anticoagulation as standard coagulation parameters are not reliable.

	Footnotes

Top Footnotes Abstract Introduction Case Reports Comment References

 
Address reprint requests to Dr Wilhelm, Klinik und Poliklinik für Thorax-, Herz- und Gefäßchirurgie, Westfälische Wilhelms-Universität, Albert-Schweitzer-Str 33, 48129 Münster, Germany.

	References

Top Footnotes Abstract Introduction Case Reports Comment References

 

1. O'Donnell BF, Tan CY. Delayed hypersensitivity reaction to heparin. Br J Dermatol 1993;129:634–6.[Medline]
2. Haram K, Hervig T, Thordarson H, Aksnes L. Osteopenia caused by heparin treatment in pregnancy. Acta Obstet Gynecol Scand 1993;72:674–5.[Medline]
3. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330–5.[Abstract/Free Full Text]
4. King DJ, Kelton JG. Heparin-associated thrombocytopenia. Ann Intern Med 1984;100:535–40.[Abstract/Free Full Text]
5. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran (Org 10172). Thromb Haemost 1993;70:554–61.[Medline]
6. Henny CP, Ten-Cate H, Ten-Cate JW, et al. A randomized blind study comparing standard heparin and a new low-molecular-weight heparinoid in cardiopulmonary bypass in dogs. J Lab Clin Med 1985;196:187–96.
7. Doherty DC, Ortel TL, De Bruijn N, Greenberg CS, Van Trigt P III. ``Heparin-free'' cardiopulmonary bypass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardiopulmonary bypass. Anesthesiology 1990;73:562–5.[Medline]
8. Salzman EW, Rosenberg RD, Smith MH, Lindon JN, Farreau L. Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 1980;65:64–73.[Medline]
9. Greinacher A, Michels I, Kiefel V, Mueller-Eckhardt C. A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost 1991;66:734–6.[Medline]
10. Greinacher A, Pötzsch B, Amiral J, Dummel V, Eichner A, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost 1994;71:247–51.[Medline]
11. Cines DB, Tomaski A, Tannenbaum S. Immune endothelial-cell injury in heparin-associated thrombocytopenia. N Engl J Med 1987;316:581–9.[Abstract]
12. Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986;67:27–30.[Abstract/Free Full Text]
13. Kappa JR, Fisher CA, Todd B, et al. Intraoperative management of patients with heparin-induced thrombocytopenia. Ann Thorac Surg 1990;49:714–23.[Abstract]
14. Munver R, Schulman IC, Wolf DJ, Rosengart TK. Heparin-induced thrombocytopenia and thrombosis: presentation after cardiopulmonary bypass. Ann Thorac Surg 1994;58:1764–6.[Abstract]
15. O-Yurvati AH, Laub GW, Southgate TJ, McGrath LB. Heparinless cardiopulmonary bypass with ancrod. Ann Thorac Surg 1994;57:1656–8.[Abstract]
16. Matsuo T, Kario K, Chikahira Y, Nakao K, Yamada T. Treatment of heparin-induced thrombocytopenia by use of argatroban, a synthetic thrombin inhibitor. Br J Haematol 1992;82:627–9.[Medline]
17. DeAnda A Jr, Coutre SE, Moon MR, et al. Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass. Ann Thorac Surg 1994;58:344–50.[Abstract]
18. Mehta DP, Yoder EL, Appel J, Bergsman KL. Heparin-induced thrombocytopenia and thrombosis: reversal with streptokinase. A case report and review of literature. Am J Hematol 1991;36:275–9.[Medline]
19. Brady J, Riccio JA, Yumen OH, Makary AZ, Greenwood SM. Plasmapheresis. A therapeutic option in the management of heparin-associated thrombocytopenia with thrombosis. Am J Clin Pathol 1991;96:394–7.[Medline]
20. Roussi JH, Houbouyan LL, Goguel AF. Use of low-molecular-weight heparin in heparin-induced thrombocytopenia with thrombotic complications. Lancet 1984;1:1183–4.[Medline]
21. Massonnet-Castel S, Pelissier E, Dreyfus G, et al. Low-molecular-weight heparin in extracorporeal circulation. Lancet 1984;8387:1182–3.
22. Horellou MH, Conrad J, Lecrubier C, et al. Persistent heparin-induced thrombocytopenia despite therapy with low-molecular-weight heparin. Thromb Haemost 1984;51:134–6.[Medline]
23. Blockmans D, Bounameaux H, Vermylen J, Verstraete M. Heparin-induced thrombocytopenia, platelet aggregation studies in the presence of heparin fractions or semi-synthetic analogues of various molecular weights and anticoagulant activities. Thromb Haemost 1986;55:90–3.[Medline]
24. Bradbrook I, Magnani HN, Moelker HCT, et al. Org 10172: a low molecular weight anticoagulant with a long half-life in man. Br J Clin Pharmacol 1987;23:667–75.[Medline]
25. Teien AN, Lie M, Abildgaard U. Assay of heparin in plasma using a chromogenic substrate for activated factor X. Thromb Res 1976;8:413–6.[Medline]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Christof Schmid Hans H. Scheld Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wilhelm, M. J. Articles by Scheld, H. H. Search for Related Content PubMed PubMed Citation Articles by Wilhelm, M. J. Articles by Scheld, H. H.