Heparin-induced thrombocytopenia (HIT)

© 2006 Schattauer GmbH, Stuttgart

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Heparin-induced thrombocytopenia (HIT) A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004 Harry N. Magnani1, Alex Gallus2 1

NV Organon, Oss, The Netherlands; 2Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia

Summary Clinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed.Treatment in 1,291 episodes was for current HIT.Thromboembolism due to HIT was present in 39.4%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder,and 351 major operations were performed.Clinical outcomes were assessed during danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the danaparoid-treated patients 83.8% survived; 63.7% had no or minor adverse events and 20.1% suffered serious non-fatal adverse events.New thromboses occurred during 9.7% of treatment episodes, and 16.4% of treatment episodes had an inadequate treatment response (i.e. developed one or more of the following: new/extended thrombosis, persistent/new platelet

count reduction, unplanned amputation during treatment and follow-up). Major bleeding was reported in 8.1% of treatment episodes.Clinical cross-reactivity of danaparoid (new/persistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event,i.e.a total of 45 patients (3.2%). Clinical outcomes of these case reports of patients given danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors,especially when a sufficient danaparoid dosing intensity was used in patients with isolated HIT.Post-operative bleeding limits danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.

Keywords Heparin-induced thrombocytopenia, danaparoid, case reports

Thromb Haemost 2006; 95: 967–81

Introduction Heparin-induced thrombocytopenia (HIT) is a relatively common immunologically mediated complication of low-molecularweight heparin and unfractionated heparin [(LMW)heparin] use where a high frequency of thrombosis causes severe morbidity and mortality (1). Danaparoid is a non-heparin, parenteral antithrombotic approved for use in HIT, deep vein thrombosis (DVT) prophylaxis and disseminated intravascular coagulopathy (DIC) (Japan only). The drug is marketed in Canada, Australia, New Zealand and most of Europe but is not available in the U.S. It inhibits thrombin generation by accelerating inactivation of factor Xa by antithrombin (AT) and inhibits thrombin activity via both AT and heparin cofactor II. Danaparoid also inhibits thrombin activation of factor IX (2). Thus, danaparoid can control the rapid thrombin generation associated with HIT (3).

In 1985 a small open prospective comparison of danaparoid plus warfarin with dextran plus warfarin in patients with HIT and a thrombosis (4) showed that clinical outcomes were superior after treatment with danaparoid and warfarin. With this exception doctors have been reluctant to consider randomised prospective evaluations of unfamiliar new therapies for HIT, so that most information about HIT treatment options comes from cohort studies that are wholly retrospective (5) or where prospective treatment outcomes with newer drugs, e.g. lepirudin (Refludan®) or argatroban (Novastan®), are compared with outcomes in historic controls given drugs no longer or now infrequently used by the authors (6, 7). The results of such studies can be misleading for many different reasons (4–7). Another way to gain information on drug efficacy and safety is to review all available case reports of its use for patients with HIT. Between 1982 and 1997 the manufacturer conducted a noncomparative compassionate-use programme to supply danapa-

Correspondence to: Dr. Harry N. Magnani Schoutstraat 54 5345 MT, Oss, The Netherlands Tel.: +31 412 639512; E-mail: [email protected]

Received July 12, 2005 Accepted after resubmission April 14, 2006 Prepublished online May 11, 2006 doi:10.1160/TH05–07–0489

967

Magnani, Gallus: Danaparoid treatment in HIT patients

roid for named-patients with HIT and other forms of heparin-intolerance (8–13). In addition, many case reports of danaparoid treatment of HIT patients were independently published during and after this period. The aim of the present analysis is to assess the place of danaparoid in the treatment of HIT by collating case reports from 1982 (14), when the first patient was treated, until mid-2004.

Methods Included case reports were those with sufficient details for adequate data extraction (i.e. clarity of demographic data, treatment period, HIT diagnostic confirmation, danaparoid crossreactivity and events relating to clinical outcome, i.e. efficacy, safety and mortality) of unique patients or patient series treated with danaparoid. All events reported during follow-up after discontinuing danaparoid have been included for each patient. Excluded case reports were those which: – provided insufficient/inadequate data, or – duplicated an included paper (e.g. alternative language publication). Three groups of case-reports were identified: Group 1: Compassionate-use programme Apart from a reasonably well founded diagnosis of HIT and a life expectancy of more than three months if HIT was successfully treated, there was no other enrolment restriction in this namedpatient programme. Group 2: Literature search A literature search of danaparoid use in HIT patients was conducted using Medline and Current Contents databases, Internet search engines such as ‘Google’, ‘Wanadoo’ and ‘Jeeves’, as well as the manufacturer’s search facilities and in-house data bases for case reports published independently of NV Organon from 1983 to mid-2004. All papers found were included except: – presentations of interim results (e.g. preliminary meeting abstract) of the included (final) paper, or interim descriptions of the patient population enrolled in the danaparoid compassionate-use programme, – descriptions of in vivo or ex vivo testing of danaparoid for cross-reactivity without its administration to a patient with HIT. Group 3: Spontaneous serious adverse event (SAE) reports Despite sometimes fragmentary data, all SAEs of HIT patients treated with danaparoid and reported to the manufacturer to mid-2004 were entered into this data-base. Definitions used in the study Current HIT Patients with serologically demonstrable (LMW)heparininduced anti-platelet antibody or with clinical (including platelet count reduction) manifestations of HIT which developed less than three months prior to the use of danaparoid.

Past HIT Patients with negative serological status and/or whose diagnosis of HIT was documented at least three months prior to the use of danaparoid. Isolated HIT HIT presenting without a thrombotic complication. Paediatric Refers to subjects aged from birth up to and including 17 years. Serious adverse event (SAE) Is one which: – is fatal or life-threatening – prolongs or leads to renewed hospitalisation – leads to (re)operation – results in persistent or significant disability. Sero-conversion Was diagnosed if: – serological test results for danaparoid cross-reactivity changed from negative prior to its use to positive during its use, – no serological test was performed before danaparoid use but a cross-reactivity test performed because of suspected clinical cross-reactivity was positive, i.e. the test was done because of a new platelet count reduction or failure of a low count to recover and/or evidence of a thrombotic event with onset during danaparoid use. Sero-conversion Was suspected if: – clinical cross-reactivity was observed in the absence of any serological testing, i.e. a new platelet count reduction or failure of a low count to recover, and/or evidence of a thrombotic event during danaparoid use, which could not be explained by a co-morbid disorder or an inadequate dosing regimen. Diagnosis of HIT Suspicion of HIT HIT was suspected in patients if an unexplained platelet count reduction or thromboembolic event occurred during (LMW)heparin treatment (particularly if events were multiple, arterial and venous or at an unusual site). Occasionally isolated thrombopenia was associated with ‘heparin resistance’[difficulty maintaining therapeutic anticoagulation despite increasing the dose of unfractionated heparin (15)]. Serological confirmation of HIT HIT was most commonly confirmed by the platelet aggregation test (PAT, or HIPA in the USA). Other tests used include the serotonin release assay (SRA) in Canada, the heparin-induced platelet activation assay (HIPAA) in Germany and the enzyme linked immuno-assay (EIA) in France. If two or more tests were used in a single patient, then HIT was considered confirmed if at least one was positive.

968


Clinical confirmation of HIT Clinical confirmation of HIT was indicated by the occurrence on rechallenge of platelet count reduction and/or white clot syndrome (WCS), and/or an acute systemic (15) or local skin (necrosis) reaction to (LMW)heparin. Occasionally one of the latter was present despite negative HIT serology. Danaparoid treatment outcome assessments Composite indicator of lack of efficacy: major efficacy outcomes (SAE’s) – fatal and non-fatal thrombotic events (new or progression) – unplanned amputations (i.e. amputations for which danaparoid was not specifically requested a priori to cover the operation) – persistent or renewed platelet count reduction – any combination of the above in one treatment episode. Composite indicator of lack of safety: major safety outcomes (SAE’s) – major bleeding (defined by any of the following: fatal or lifethreatening, led to operation or required more than two or more units of blood or other blood product transfusion if medical, or led to re-operation or more than two units of blood or other blood product transfusion if surgical or required discontinuation of danaparoid, or led to rehospitalisation or to significant or persistent disability) – all other causes of mortality (excluding deaths due to thrombotic or major bleeding events) – worsening of or new skin rash – other non-fatal adverse events leading to danaparoid discontinuation – any combination of the above in one treatment episode. Additional assessments – survival at the end of the follow-up period – minor bleeding (which did not satisfy the criteria for major bleeding and which did not require danaparoid discontinuation) – danaparoid cross-reactivity prior to treatment initiation – sero-conversion – both serological and clinical. Statistics Demographic, efficacy and safety parameters were summarised and tabulated, but no formal statistical analyses were made.

Literature search (Group 2) Two hundred twenty-two acceptable publications (1, 3, 6, 13, 16-232) and an unpublished communication from Keen RR, Durham JR, Green D (1997) were identified. They comprise 200 with individual patient(s) data, 20 papers each summarising a unique series of patients treated with danaparoid and two papers where most patients were excluded because of lack of detail, but one or two sufficiently well described patients were identified. In total, adequate data was identified in these 20 patient series on 378 individual cases and 334 cases in total, i.e. 712 treatment episodes for 699 patients in total. Thirty-six publications (5, 8–13, 233–261) were excluded because 21 appeared to duplicate cases included in other papers from the same authors (some of which were alternative language publications) and 15 mentioned danaparoid use but lacked sufficient clinical detail. Spontaneous serious adverse (SAE) event reports (Group 3) Ninety-two unsolicited reports of SAEs in HIT patients were received by the manufacturer during the review period. Four were identified with published cases and are included in Group 2, leaving 88 cases for Group 3. Number of HIT patients treated with danaparoid World-wide over 100,000 HIT patients have been treated outside the compassionate-use programme since the first approval for danaparoid use for HIT. However, because the actual number is uncertain, outcome frequencies of the various treatment endpoints are derived using the total number of reported patients (n = 1,418) or treatment episodes (n = 1,478, since 51 patients had more than one episode of treatment) as appropriate. Demographic data and HIT diagnosis Demographic data is summarised in Table 1. Current HIT was diagnosed in 1,283 of the 1,478 treatment episodes (86.8%). Laboratory confirmation of HIT (Table 2) was reported for 1,099/1,418 (77.5%) of the patients. Negative HIT serology was recorded in 8.1% of those tested. HIT was confirmed clinically in some serologically negative or untested patients by observing platelet count reduction after heparin rechallenge and/or white clot syndrome or rarely an acute anaphylactic reaction (14) to heTable 1: Demographic data.

Results In total, 1,478 case reports were found for 1,418 patients. Compassionate use programme (Group 1) Six hundred seventy-eight treatment episodes in 631 patients were identified as unique to this database. An additional 82 case reports for 80 patients from this programme were also identified in 29 independent publications and two spontaneous adverse event reports. Their data were analysed with those of the Group 2 and Group 3 patients, respectively.

969

Parameter

Group 1

Group 2

Group 31

Number of – All treatment episodes – Repeat danaparoid uses – Patients

678 47 (39)4 631

712 13 (12)4 699

88 0 88

61 (90 kg. These recommendations are now mentioned in national authorisations of marketing for danaparoid. We would also recommend checking plasma anti-Xa activity at least every 1 – 2 months during chronic use, even if the patient appears problem free. Recommendations for optimal danaparoid use The collated data supports the following recommendations for optimal treatment with danaparoid in clinically suspected HIT: – the diagnosis should be serologically confirmed, and a pretreatment blood sample should be tested for danaparoid cross-reactivity. It is not necessary to wait for the result of either test before initiating danaparoid therapy (267, 293). However, if the pre-treatment danaparoid cross-reactivity test is positive, we advise switching to alternative suitable antithrombotic replacement therapy with few exceptions (see discussion). – the initial danaparoid dosing intensity should be sufficient to be effective during this early highly thrombophilic period (1, 7, 267). The patient’s high thrombotic risk in the absence of any antithrombotic therapy must be balanced against the bleeding risk and/or need for early surgery (15). – plasma anti-Xa activity monitoring should be considered if the patient is >90 kg or 30 ml/minute). In these cases and once the plasma anti-Xa activity is stable and within the target range, the monitoring interval can be extended unless the patient’s clinical status deteriorates. – we recommend platelet count monitoring daily during the first week of danaparoid administration, on alternate days during the next two weeks and then on a weekly basis while danaparoid administration continues. During chronic danaparoid use a platelet count should be performed at least once every 1 – 2 months. If the patient’s pre-treatment danaparoid cross-reactivity test was positive, then the daily platelet count should be continued for at least two weeks. – if the onset of clinical cross-reactivity is suspected during danaparoid therapy, then a test should be made for sero-conversion. Inadequate dosing and possible differential diagnoses of thrombophilia and/or thrombocytopenia (273), e.g. sepsis, concomitant drugs, DIC, APL (and related syndromes) or pseudothrombocytopenia (272) etc., some of which may also delay platelet count recovery, should be excluded. If in doubt, then danaparoid therapy should be withdrawn. – patients with confirmed clinical danaparoid cross-reactivity should carry a warning against its future use.

975


Conclusions – This analysis of 1,478 reports of danaparoid treatment for HIT has found it to be safe and effective in patients of all ages with a wide range of co-morbid clinical problems and antithrombotic requirements. – Patients with isolated HIT (no thromboembolic complications at diagnosis) should receive the highest recommended prophylactic dosing intensity compatible with their risk of bleeding because of their high risk of developing thrombosis.

– Danaparoid is generally unsuitable during surgery that requires cardiopulmonary bypass. – Although danaparoid treatment has apparently successfully treated some patients with serologically proven cross-reactivity to the LMW heparin-induced anti-platelet antibody, the patient should be switched to another alternative antithrombotic if a suitable one is available. – Patients with clinical danaparoid cross-reactivity should carry a warning against its future use.

References 1. Boshkov LK, Warkentin TE, Hayward CPM, et al. Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies. Br J Haematol 1993; 84: 322–8. 2. Ofosu FA. Anticoagulant mechanisms of Orgaran (Org 10172) and its fraction the high affinity to antithrombin III (Org 10849). Haemost 1992; 22: 66–72. 3. Chong BH, Gallus AS, Cade JF, et al. Prospective open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopenia with thrombosis. Thromb Haemost 2001; 86: 1170–5. 4. Warkentin TE. Limitations of conventional treatment options for heparin-induced thrombocytopenia. Seminars in Haematology, 1998; 35 (Suppl 5): 17–25. 5. Warkentin TE. The treatment of heparin-induced thrombocytopenia (HIT): An historical comparison of ancrod versus danaparoid in one medical community. 65th RCPSC meeting abstract in Clin Invest Med 1996; 19 (Suppl S31): No. 240. 6. Greinacher A, Janssens U, Berg G, et al. Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-induced thrombocytopenia study (HAT) investigators. Circulation 1999; 100: 587–93. 7. Farner B, Eichler P, Kroll H, et al. A comparison of lepirudin and danaparoid in patients with heparin-induced thrombocytopenia (HIT). Thromb Haemost 2001; 85: 950–7. 8. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaran® (Org 10172). Thromb Haemost 1993; 70: 554–61. 9. Magnani HN. Orgaran® (danaparoid) use in the syndrome of heparin-induced thrombocytopenia. Platelets 1997; 8: 74–81. 10. Ortel TL, Chong BH. New treatment options for heparin-induced thrombocytopenia. Sem Hematol 1998; 35 (Suppl 5): 26–34. 11. Chong BH, Magnani HN. Orgaran® in heparin-induced thrombocytopenia. Haemost 1992; 22: 85–91. 12. Chong BH, Magnani HN. Danaparoid for the treatment of heparin-induced thrombocytopenia. In: Heparin-induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 371–96. 13. Magnani HN, Beyering R, Cate JW ten, et al. Orgaran® anticoagulation for cardiopulmonary by-pass in patients with heparin-induced thrombocytopenia. In: New anticoagulants for the cardiovascular patient. Pifarre R, Publ Hanley and Belfus Inc. Philadelphia, 1997; 487–500. 14. Harenberg J, Zimmermann R, Schwartz F, et al. Treatment of heparin-induced thrombocytopenia with thrombosis by a new heparinoid. Lancet 1983; 30: 986–7.

15. Warkentin TE. Clinical picture of heparin-induced thrombocytopenia. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 53–106. 16. Alkindi S, Enright H. Successful therapy of heparin induced thrombocytopenia with alternative anticoagulants. Ir J Med Sci 1999; 168 (Suppl 3): 29 (Abstr P 94). 17. Alvarez JM, Mezzatesta JP. Aprotinin and Organon 10172: a successful combination for coronary artery bypass surgery complicated by heparin-induced thrombocytopenia. Aust NZ J Surg 2000; 70: 819–21. 18. Amberger HG. Heparininduzierte Thrombozytopenie Typ II mit thromboembolischen Komplikationen. Med Welt 1999; 50: 13–5. 19. Andolfatto S, Latger-Cannard V, de Maistre E, et al. Nécroses cutanées induites par l’héparine à propos de deux cas. Ann Biol Clin 2001; 59: 651–4. 20. Anon. Heparin-induced thrombocytopenia (HIT) and new anticoagulant and antithrombotics. Case. Pharmacy Nursing Inservice 2002. 21. Anon. ‘Today I turned 5’. Personal account. Available at www.deardiary.net. March 18, 2002. 22. Aoufi A, Blanc P, Piriou V, et al. Cardiac surgery with cardiopulmonary bypass in patients with Type II heparin-induced thrombocytopenia. Ann Thorac Surg 2001; 71: 678–83. 23. Ariano RE, Bhattcharya SK, Moon M, et al. Failure of danaparoid anticoagulation for cardiopulmonary bypass. J Thorac Cardiovasc Surg 2000; 119: 267–8. 24. Arnheim K. Diagnostische und therapeutische Massnahmen bei Heparin-induzierter Thrombozytopenie II. Haemostasiologie 2000; 20: 50–2. 25. Asztely M, Larsson B, Lindgren A, et al. Komplikation vid Budd-Chiari Syndrom, Heparinbehandling orsakade trombocytopeni. Läkartidningen, 1994; 91: 3499–502. 26. Barratt S McG, Ruff SJ, et al. Heparin-induced thrombocytopenia presenting after the cessation of low molecular weight heparin prophylaxis with enoxaparin. MJA 2000; 172: 449. 27. Barth KSA. Inzidenz der Heparin-induzierten Thrombozytopenie Typ II am Klinikum der Justus-Liebig-Universität Giessen. MD Thesis, Giessen 1998. 28. Baumgartel MW, Eichler P, Glockner W, et al. Heparin-induced thrombocytopenia (HIT): in vitro and in vivo cross-reactivity to danaparoid sodium and successful treatment with recombinant hirudin (lepirudin). (Letter) Eur J Haematol 2000; 65: 148–9. 29. Beland B, Busse H, Loick HM, et al. Phlegmasia cerulea dolens, cerebral venous thrombosis and fatal pulmonary embolism due to heparin-induced thrombocytopenic thrombosis syndrome. Anesth Analg 1997; 85: 1272–4. 30. Ben Ami R, Rachmimov S, Berliner S. Danaparoid sodium for dialysis in heparin-induced thrombocytopenia. Harefuah 1999; 136: 361–4, 419.

976

31. Benedetti-Bardet C, Chaussinand JP, Tardy B, et al. Thrombopenia with thrombosis with heparin and Danaparoid about a fatal evolution case. (Letter) Therapie 1999; 54: 297. 32. Bergeron S, Demers C, Bogarty P, et al. The endocarditis that was not: an unusual case of heparin-induced thrombocytopenia with unusual complications. Can J Cardiol 2001; 17: 1180–2. 33. Besien K van, Hoffman R, Golichowski A. Pregnancy associated with lupus anticoagulant and heparininduced thrombocytopenia: management with a low molecular weight heparinoid. Thromb Res 1991; 62: 23–9. 34. Blakeman B. Management of heparin-induced thrombocytopenia: a cardiovascular surgeon’s perspective. Sem Hematol 1999; 36 (Suppl 1): 37–41. 35. Bleasel JF, Rasko JEJ, Rickard KA, et al. Acute adrenal insufficiency secondary to heparin-induced thrombocytopenia-thrombosis syndrome. Aust Med J 1992; 157: 192. 36. Bocquet R, Blanot S, Dautzenberg MD, et al. Syndrome des anticorps antiphospholipides en neurochirurgie pédiatrique: un probleme d’hémostase. Ann Fr Anesth Réanim 1999; 18: 991–5. 37. Bondoc AY, Kapoor M. Successful thrombolysis for heparin-induced thrombocytopenia and thrombosis after hepatic resection. Chest 2000; 118 (Suppl 4): Abstr 291S. 38. Boon DM, Michiels JJ, Stibbe J, et al. Heparin-induced thrombocytopenia and antithrombotic therapy. (Letter) Lancet 1994; 344: 1296. 39. Boon DM, Kappers-Klunne MC, Michiels JJ, et al. Heparin-induced thrombocytopenia and thrombosis: a potential fatal complication in a routine treatment. Neth J Med 1995; 46: 146–52. 40. Boshkov LH, Hamilton P, Lee A, Boldt K. Successful therapy of heparin-induced thrombocytopenia with thrombosis (HITTS) in pregnancy with danaparoid sodium. Blood 1999; 94 (Suppl 1): 102b. 41. Bredlich RO, Stracke S, Gall H, et al. Heparinassoziertes Thrombozyten-Aggregationssyndrom mit Hautnekrosen bei Hämodialyse. Dtsch med Wschr 1997; 122: 328–32. 42. Bremaud M, De Maistre E, Junke E, et al. Peri-operative anticoagulation with danaparoid for a patient with Budd-Chiari syndrome and heparin-induced thrombocytopenia. Ann Fr Anesth Reanim 2004; 23: 50–5. 43. Bretelle RO, Leude E. Quilici J, et al. Utilisation de l’Orgaran® pour une circulation extra-corporelle chez une patiente allergique a l’héparine. Presse Méd 1996; 25: 1847. 44. Brimhall DB. Heparin-induced thrombocytopenia and thrombosis, the “white clot syndrome”. Poster presented at the ASIM-Missouri 2000. Available at http://www.amsect.org/ce/HIT/HITPoster.htm.

Magnani, Gallus: Danaparoid treatment in HIT patients 45. Buerger T, Tautenhahn J, Meyer F, et al. Heparin-induced vascular occlusion in vasculosurgical patients – an evaluation of the disease in 13 patients. J Cardiovasc Surg 1999; 40: 237–42. 46. Buerkhard-Meier U, Soehngen D, Schultheiss H-P, et al. Heparin-induced thrombocytopenia Type II: successful use of Orgaran® (Org 10172) in intensive care patients. Intensive Care Med 1995; 21: 542–4. 47. Burke AP, Mezzetti T, Farb A, et al. Multiple coronary graft occlusion in a fatal case of heparin-induced thrombocytopenia. Chest 1998; 114: 1492–5. 48. Buys S, Duterque D, Rouge P, et al. The use of danaparoid sodium in patients with heparin-induced thrombocytopenia requiring cardiac surgery with cardiopulmonary bypass is detrimental: a matched case control study. Anesthesiology 2003; 99: A-223. 49. Cannell PK, Herrmann RP, Marshall L. Heparinoid during cardiopulmonary by-pass. Aust NZ J Med 1991; 21 (Suppl 1): 141. 50. Cantor WJ, Leblanc MD, Garvey, et al. Combined use of Orgaran® and Rheopro® during coronary angioplasty in patients unable to receive heparin. Catheter Cardiovasc Interv 1999; 46: 352–5. 51. Chong BH, Ismail F, Cade J, et al. Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172. Blood 1989; 73: 1592–6. 52. Christiansen S, Jahn UR, Meyer J, et al. Anticoagulative management of patients requiring left ventricular assist device implantation and suffering from heparininduced thrombocytopenia Type II. Ann Thorac Surg 2000; 69: 774–7. 53. Christiansen S, Geiger A, Splittgerber FH, et al. Coronary artery by-pass grafting in a patient with type II heparin associated thrombocytopenia. Cardiovasc Surg 1998; 6: 90–3. 54. Christin F, Thiessen-Lavat O, Loeb JP. Intérêt du danaparoïde (Orgaran®) au cours de l’hémofiltration veinoveineuse continue en présence d’une thrombopénie a l’héparine. Ann Fr Anesth Reanim 1998; 17: 82–3. 55. Cicco NA, Gerkin G, Frey M, et al. Heparin-induced thrombocytopenia. Intensivmed 2000; 37 (Suppl 1): I/99-I/107. 56. Collart F, Derouck D, Kerbaul F, et al. Regression of intracardiac heparin-induced thrombosis after aortic root surgery. Ann Thorac Surg 2003; 76: 617–9. 57. Dandekar U, Young J, Kalkat M, et al. Heparin-induced thrombocytopenia type II complicating coronary artery bypass surgery: a tale of caution. Interact Cardiovasc Thorac Surg 2004; 3: 121–3. 58. Darling K, Jaumotte C, Saussoy P, et al. Heparin-induced thrombocytopenia complicated by arterial and venous thrombosis: report of 2 cases successfully treated by danaparoid sodium. Acta Clin Belg 2000; 55: 176–81. 59. Davenport A. Management of heparin-induced thrombocytopenia during continuous renal replacement therapy. Am J Kidney Dis 1998; 32: E3. 60. Davidson SJ, Burman JF, Chaubey S, et al. A patient with factor V Leiden who rapidly developed fatal heparin-induced thrombocytopenia. Thromb Haemost 2003; (Suppl 1): Abstr No. P1170. 61. Deryck YL, van Krugten RJ, Schepp RM, et al. Heparinoid Org 10172 for anticoagulation during extracorporeal circulation: a case report. Acta Anaesthesiologica Belg 1990; 41: P54 . 62. Doherty DC, Ortel TL, Bruijn N de, et al. Heparinfree cardiopulmonary by-pass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardio-pulmonary by-pass.Anesthesiol 1990; 73: 562–5. 63. Dworschak M, Hiesmayr JM, Lassnigg A. Lifesaving citrate anticoagulation to bridge to danaparoid treatment. Ann Thorac Surg 2002; 73: 1626–7.

64. Elalamy I, Lecrubier C, Potevin F, et al. Danaparoid therapy and cross-reactivity: study of 117 HIT patients. Thromb Haemost 2000; 30 (Suppl 1): 64. 65. Elzo-Kraemer CV, Sijpkens YWJ, Huisman MV. Finger gangrene, adrenal haemorrhage and deep venous thrombosis in a woman with heparin-induced thrombocytopenia (HIT) type II syndrome. Neth J Med 2002; 60: Abstr 99. 66. Emig U, Meyer T, Buchwald AB. Erfolgreiche lysetherapie einer Vena-cava Inferior and Iliofemoral Venenthrombose bei Heparin-induzierte Thrombozytopenie Typ II. Dtsch med Wschr 1997; 122: 965–8. 67. Espiritu JD, Creer MH, Miklos AZ, et al. Fatal tumour thrombosis due to an inferior vena cava leiomyosarcoma in a patient with antiphospholipid syndrome. Mayo Clin Proc 2002; 77: 595–9. 68. Fernandes P, Mayer R, MacDonald JL, et al. Use of danaparoid sodium (Orgaran®) as an alternative to heparin sodium during cardiopulmonary bypass: a clinical evaluation of six cases. Perfusion 2000; 15: 531–9. 69. Fischer KG, Karger R, Nies C, et al. Heparin-induzierte Thrombozytopenie mit Todesfolge nach vorderer Exenteration wegen Harnblasenkarzinom bei SharpSyndrom– ein Fallbericht. Akt Urol 1998; 29: 39–42. 70. Flamholz R, Tran T, Grad GI, et al. Therapeutic plasma exchange for for the acute management of the catastrophic antiphospholipid syndrome: β2-glycoprotein I antibodies as a marker as a response to therapy. J Clin Apheresis 1999; 14: 171–6. 71. Francis JL, Palmer GJ, Moroose R, et al. Comparison of bovine and porcine heparin in heparin antibody formation after cardiac surgery. Ann Thorac Surg 2003; 75: 17–22. 72. Gailani D, Reese EP. Anticoagulant-induced skin necrosis with hereditary deficiency of Protein S. Am J Hematol 1999; 60: 231–6. 73. Gerhardt A, Zotz RB, Scheja JW, et al. First successful use of danaparoid in a pregnant woman with tricuspid valve prosthesis and heparin-induced thrombocytopenia Type II (HIT TYP II). Blood 2000; 96: 95B Abstr 4093 [and abstract in Ann Hematol 2001; 80 (Suppl 1): A20]. 74. Gill J, Kovacs MJ. Successful use of danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy. Obstet Gynecol 1997; 90: 648–50 [and abstract in Blood 1996; 88 (Suppl 1) No 3053]. 75. Gillis S, Gideon M, Zahger D, et al. Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced thrombocytopenia. B J Haematol 1997; 98: 657–9. 76. Gindre I, Maistre E de, Perrin A, et al. Thrombopénies sous héparinothérapie. Utilisation du danaparoïde (Orgaran), trieze cas monocentriques sous le régime de l‘ATU. Thérapie 1997; 52: 591–7. 77. Girisch M, Buheitel G, Ries M, et al. Safe and effective use of danaparoid during cardiac catheterization in a 14 month old boy with tetralogy of Fallot and heparin-induced thrombocytopenia. Ann Hematol 2001; 80 (Suppl): A20 Abstr 68. 78. Bidlingmaier C, Magnani HN, Girisch M, et al. Safety and efficacy of danaparoid (Orgaran) use in children. Acta Haematol 2006; 115: 237-47. 79. Gitlin SD, Deeb GM, Yann C, et al. Intraoperative monitoring of danaparoid sodium anticoagulation during cardiovascular operations. J Vasc Surg 1998; 27: 568–75. 80. Godet G, Bertrand M, Steen E van de, et al. Danaparoïde and heparin-induced thrombocytopenia. Ann Fr Anesthesie Reanim 2001; 20: 50–3. 81. Goti F, Gianom D, Korte W, et al. Postoperative heparin-induzierte thrombopenie mit thromboembolie (HITT) – eine seltene Komplikation der Heparintherapie. Swiss Surg 2001; 7: 51–6.

977

82. Gottschling LL, Alaniz C. Thrombosis resulting from heparin therapy. Pharmacotherapy 1996; 16: 469–72. 83. Gould J, Myers B. Prophylactic danaparoid in heparin-induced thrombocytopenia presenting with skin manifestations in pregnancy. Blood Coag Fibrinol 2002; 13: Abstr P15. 84. Goyen M, Kroger K, Massalha K, et al. Schwierigkeiten in der Erkennung der Heparin-induzierten Thrombozytopenie Typ II. Schweitz Rundsch Med Praxis 1999; 88: 458–90. 85. Grainger JD, Hay CRM. Heparin induced thrombocytopenia caused by danaparoid sodium. Abstract CD3458 presented at the 18th ISTH congress. Thromb Haemost 2001; available on CD-ROM. 86. Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: The antibody is not heparin specific. Thromb Haemost 1992; 67: 545–9. 87. Greinacher A, Drost W, Michels I, Leitl J, et al. Heparin associated thrombocytopenia: successful therapy with a heparinoid (Org 10172) in a patient showing cross-reaction to LMW heparins. Ann Hematol 1992; 64: 40–2. 88. Greinacher A, Philippen KH, Kemkes-Mathes B, et al. Heparin-associated thrombocytopenia type II in a patient with end-stage renal disease: successful anticoagulation with the low molecular weight heparinoid Org 10172 during haemodialysis. Nephrol Dial Transplant 1993; 8: 1176–7. 89. Greinacher A, Eckhardt Th, Mussmann J, et al. Pregnancy complicated by heparin-associated thrombocytopenia: management by a prospectively in-vitro selected heparinoid (Org 10172). Thromb Res 1993; 71: 123–6. 90. Grocott HP, Root J, Berkowitz SD, et al. Coagulation complicating cardiopulmonary by-pass in a patient with heparin-induced thrombocytopenia receiving the heparinoid danaparoid sodium. J Cardiothorac Vasc Anesth 1997; 11: 875–7. 91. Gruel Y, Nguyen P, Pouplard C, et al. Low molecular weight heparin-induced thrombocytopenia: different from HIT due to unfractionated heparin. Blood 2000; 96: 272a-273a. 92. Haas S. Chirurgische und internistische Fallbeispiele zur HIT II. J Anasth Intensivbehandl 2000; 7: 27–30. 93. Haas S. Fallbeispiele zur Therapie der HIT II aus gutachterlicher Sicht. Anaesth Intensiv Notfallmed Schmerzther 2002; 37 (Suppl 1): 17–9. 94. Hach-Wunderle V, Hach W. Die Konsultation der Chirurgen bei der Kumarinnekrose. Gefässchirurgie 1996; 1: 241–6. 95. Hach-Wunderle V, Kainer K, Salzmann G, et al. Heparin-related thrombosis despite normal platelet counts in vascular surgery. Am J Surg 1997; 173: 117–9. 96. Hach-Wunderle V, Kainer K, Krug, et al. Heparin associated thrombosis despite normal platelet counts. The Lancet 1994; 344: 469–70 97. Hale LP, Smith K, Braden GA, et al. Orgaran® during rotational atherectomy in the setting of heparin-induced thrombocytopenia. Catheter Cardiovasc Diagn 1998; 45: 318–22. 98. Harbrecht UM, Weber D, Hertfelder H-J, et al. Low molecular weight heparin causing heparin-induced thrombocytopenia type II with severe thrombotic complications. 42nd Ann Meeting GTH 1998: Abstr P-127. 99. Harenberg J, Huhle G, Piazolo L, et al. Anticoagulation in patients with heparin-induced thrombocytopenia type II. Semin Thromb Hemost 1997; 23: 189–96. 100. Henny ChP, Cate H ten, Cate JW ten, et al. Thrombosis prophylaxis in an AT-III deficient woman: application of a low molecular weight heparinoid. Thromb Haemost 1986; 55: 301.

Magnani, Gallus: Danaparoid treatment in HIT patients 101. Hermanns B, Janssens U, Handt S, et al. Pathomorphological aspects of heparin-induced thrombocytopenia II (HIT-II syndrome). Virchows Arch 1998; 432: 541–6. 102. Herzog S, Rath W, Kuhn W. Successful therapy of heparin associated thrombocytopenia with a low grade sulphated heparinoid. Geburtsh Frauenheilk 1995; 55: 154–6. 103. Hill GR, Hickton C, Henderson S, et al. The use of low dose Orgaran® in heparin-induced thrombocytopenia associated with in-vitro platelet aggregation at higher Orgaran concentrations. Clin Lab Haem 1997; 19: 155–7. 104. Hobbensiefken G, Driller B, Studtmann, et al. Eine fatale Komplikation der medikamentösen Thromboprophylaxe mit Heparinen. Unfallchirurgie 1996; 22: 248–52. 105. Hofbauer LC, Spitzweg C, Heufelder AE. Grave’s disease associated with primary antiphospholipid syndrome. J Rheumatol 1996; 23: 1435–7. 106. Hoffmann, Huhle G, Haseroth K, et al. A fatal complication in a patient with heparin-induced thrombocytopenia type II re-exposed to heparin. Eur J Orthop Surg Traumatol 1999; 9: 205–7. 107. Horellou MH, Elalamy I, Achkar A, et al. Efficacy and safety of danaparoid (Orgaran®) in venous thrombosis in pregnant women with thrombophilia and heparin-induced thrombocytopenia. Thromb Haemost 2001; Suppl for XVIII ISTH: Abstr P2997. 108. Houltz B, Gudnasson T, Tengborn L. Heparinbehandling gav trombocytopeni. Lakartidningen 1997; 94: 416–9. 109. Huiet III F, Campbell CL, Grathwohl K, et al. Heparin-induced thrombocytopenia manifest as vena cava syndrome. South Med J 2000; 93: S41–2. 110. Insler SR, Kraenzler EJ, Bartholomew JR, et al. Thrombosis during the use of heparinoid Organon 10172 in a patient with heparin-induced thrombocytopenia. Anaesth 1997; 86: 495–8. 111. Jackson MR, Danby CA, Alving BM. Heparinoid anticoagulation and topical fibrin sealant in heparin-induced thrombocytopenia. Ann Thorac Surg 1997; 64: 1815–7. 112. Jakobs D. Heparininduzierte Thrombozytopenie, Ventrikelthrombus und zerebrale Embolie im Verlauf eines akuten Myokardinfarkts. Med Klin 2001; 96: 101–4. 113. Janssens U, Breithardt OA, Greinacher A. Successful thrombolysis of right atrial and ventricle thrombi encircling a temporary pacemaker lead in a patient with heparin-induced thrombocytopenia. Pacing Clin Electrophysiol 1999; 22: 678–81. 114. Janssens U, Klues HG, Greinacher A, et al. Severe arterial and venous thromboses in a patient with heparin-induced thrombocytopenia type II. Intensive Care Med 1997; 23: 595–6. 115. John G, Shehabi Y, Mudaliar Y. Use of a low molecular weight preparation of heparin – Org 10172 (Lomoparan) in the critically ill. Anaesth Intensive Care 1991; 19: 588–91. 116. Kadidal W, Mayo DJ, Horne MK. Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases. L Int Med 1999; 246: 325–9. 117. Kanagasabay RR, Unsworth-White MJ, Robinson G, et al. Cardiopulmonary bypass with danaparoid sodium and ancrod in heparin-induced thrombocytopenia. Ann Thorac Surg 1998; 66: 567–9. 118. Keeling DM, Richards EM Baglin TP. Platelet aggregation in response to four low molecular weight heparins and the heparinoid Org 10172 in patients with heparin-induced thrombocytopenia. Br J Haematol 1994; 86: 425–6. 119. Keng B, Chong BH. Heparin-induced thrombocytopenia and thrombosis syndrome: in vivo cross-reac-

tivity with danaparoid and successful treatment with r-hirudin. B J Haematol 2001; 114: 394–6. 120. Kiers L, Grigg LE, Cade JF, et al. Use of Org 10172 in the treatment of heparin-induced thrombocytopenia and thrombosis.Aust NZ J Med 1986; 16: 719. 121. Kleinschmidt S, Seyfert UT. Heparin-associated thrombocytopenia (HAT) – still a diagnostic and therapeutical problem in clinical practice. Angiology 1995; 46: 37–44. 122. Kleinschmidt S, Ziegenfuss T, Seyfert UT, et al. Septisch-toxisches Herz-Kreislauf-Versagen als Folge einer Heparin-induzierten Thrombozytopenie mit “White Clot Syndrome”. Anaesth Intensivmed Notfallmed Schmerzther 1993; 28: 58–60. 123. Klement D, Rammos S, van Kries R, et al. Heparin as a cause of thrombus progression. Eur J Pediatr 1996; 155: 11–4. 124. Klenner AF , Lubenow N, Raschke R, et al. Heparin-induced thrombocytopenia in children. Thromb Haemost 2004; 91: 719–24. 125. Kodityal S, Manhas AH, Udden M, et al. Danaparoid for heparin-induced thrombocytopenia: an analysis of treatment failures. Eur J Haematol 2003; 109–13. 126. Kollig E, Möllenhoff G, Wick M, et al. Wertigkeit der lokoregionalen Fibrinolyse von arteriellen Verschlüssen bei Heparin-induzierter Thrombozytopenie. Gefasschirurgie 1998; 3: 212–7. 127. Kollig E, Senkal M, Hentsch S, et al. Heparin-induced thrombocytopenia (HIT) during continuous veno-venous haemofiltration. Acta Anaesth Scand 1997; 41: 354, Abstr 096. 128. Krenzien J, Gussmann A. Die Heparininduzierte Thrombopenie: Beobachtungen im eigenen Kranrengut. Zentralbl Chir 1999; 124: 230–3. 129. Kuhn B. Heparin-induzierte Thrombozytopenie – eine ernstzunehmende Komplikation im Rahmen einer Heparin Therapie. Unfallchirurg 1997; 100: 646–51. 130. Lam F, Hussein S, Li P. Case Reports: Limb loss following the use of heparin. J Bone Joint Surg 2001; 83-B: 588–9. 131. Lamriben L, Tiberghien F, Delacour JL, et al. Intérêt de l’Orgaran en hémodialyse au cours d’une thrombopénie a l’héparine. Presse Méd 1996; 25: 1303. 132. Langenfeld H. Heparin-induzierte Thrombopenie vom Typ II bei einem Patienten mit schwerer Grundkrankheit. Haemostasiologie 2001; 21: 186–8. 133. Langenfeld H. Heparin-induzierte Thrombopenie – Ein fast fataler Verlauf bei einem Patienten. Anasthesiol Intensivmed 2000; 41: 542–4. 134. Larson L, Helms E, Garcia M, et al. Heparin-induced thrombocytopenia and thrombosis. Lab Med 1999; 30: 642–5. 135. Lemesle FG, Mebroukine L, Ermacora P, et al. Thrombose, thrombopénie sous HBPM et délivrance. Presse Méd 1998; 27: 19. 136. Lillo-LeLouet A, Lasne D, Chamoun K, et al. Heparin-induced thrombocytopenia (HIT) revisited. Therapie 1998; 53: 177. 137. Lindhoff-Last E, Betz C, Bauersachs R. Use of a low molecular weight heparinoid (danaparoid sodium) for continuous renal replacement therapy in intensive care patients. Clin Appl Thromb Hemost 2001; 7: 300–4. 138. Lindhoff-Last E, Bauersachs R. Heparin-induced thrombocytopenia: alternative anticoagulation in pregnancy and lactation. Seminars Thromb Haemost 2002; 28: 439–45. 139. Lischetski G, Dittrich K, Topf H-G, et al. Pediatric heparin-induced thrombocytopenia type II on dialysis. Haemostaseologie 2004; 24: A48, Abstr P38. 140. Lubenow N, Selleng S, Eichler P, et al. Cardiopulmonary bypass in patients with a history of heparin-induced thrombocytopenia: heparin re-exposure and

978

peri-operative use of danaparoid, lepirudin and argatroban.Ann Hematol 2001; 80 (Suppl 1): A44, Abstr 163. 141. Lubenow N, Eichler P, Albrecht D, et al. Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia: report of four cases and review of the literature. Thromb Res 2000; 100: 115–25. 142. Macchi L, Sarfati R, Guicheteau M, et al. Thromboembolic prophylaxis with danaparoid (Orgaran®) in a high thrombosis risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widal’s disease. Clin Appl Thromb Haemost 2000; 6: 187–9 [and as abstract in Thromb Haemost 1999; 82 (Suppl)]. 143. Mahmmod N, Hustinx WNM. Skin necrosis distant to the site of injection of low molecular weight heparin (LMWH) in association with heparin-induced thrombocytopenia (HITT). Neth J Med 2002; 60: 81 Abstr 76. 144. Mahul Ph, Raynaud, Favre JP, et al .Thrombopénie a l’héparine: sous hemodialyse en reanimation: utilisation d’un héparinoïde de bas poids moleculaire I’Org 10172 (Orgaran®). Ann Fr Anesth Reanim 1995; 14: 29–32. 145. Maistre de. 2001 Organon France marketing document. 146. Maitra RT, Scheffold N, Cyran J. Heparin-induzierte Thrombozytopenie Typ II als schwerwiegende Komplikation in der Intensivmedizin. Intensivmed Notfallmed 1997; 34: 797–802. 147. Mar AWY, Dixon B, Ibrahim K, et al. Skin necrosis following subcutaneous heparin injection. Aust J Dermatol 1995; 36: 201–3. 148. Meer ZF, Morgan S, Belli AM. Case of the month: Don’t be a clot! B J Radiol 2001; 74: 877–8. 149. Mims MP, Manian P, Rice L. Acute cardiorespiratory collapse from heparin: A consequence of heparininduced thrombocytopenia. Blood 2002; 100 (Suppl): Abstr 81b. 150. Moonen M, Rorive G. Low molecular weight heparinoid Org 10172 (danaparoid) during continuous veno-venous haemofiltration in patients with heparininduced thrombocytopenia. Nephrol Dial Transplant 1997; 12: A169. 151. Morewood GH. Uncomplicated heparinization for cardiopulmonary bypass in a patient with antiheparin antibodies. J Cardiothorac Vasc Anesth 2000; 14: 309–11. 152. Morsdorf S, Pistorius C, Orthleb R, et al. Late onset of heparin-induced thrombocytopenia with recurrent arterial thromboses and amputation. Dtsch med Wschr 1999; 124: 1271–4. 153. Muhm M, Claeys L, Huk I, et al. Thromboembolic complication in a patient with heparin-induced thrombocytopenia (HIT) showing cross-reactivity to a low molecular weight heparin–treatment with Org 10172 (Lomoparan). Wien Klin Wschr 1997; 109: 128–31. 154. Neuhaus TJ, Goetschel P, Schmugge M, et al. Heparin-induced thrombocytopenia type II in hemodialysis: switch to danaparoid. Pediatr Nephrol 2000; 14: 713–6. 155. Newall F, Barnes C, Ignjatovic V, et al. Heparininduced thrombocytopenia in children. J Paediatr Child Health 2003; 39: 289–92. 156. Newman PM, Swanson RL, Chong BH. Heparininduced thrombocytopenia: IgG binding to PF4 heparin complexes in the fluid phase and cross-reactivity with low molecular weight heparin and heparinoid. Thromb Haemost 1998; 80: 292–7. 157. Neyns B, Hubloue I, Kemp H von, et al. Unusual presentation of heparin-induced thrombocytopenia in a patient with inherited activated Protein C resistance. Acta Clin Belg 1998; 53: 293–4.

Magnani, Gallus: Danaparoid treatment in HIT patients 158. Ng T, Tillyer ML. Warfarin induced skin necrosis associated with factor V Leiden and protein S deficiency. Clin Lab Haem 2001; 23: 261–4. 159. Nguyen TN, Gal P, Ransom JL, et al. Lepirudin use in a neonate with heparin-induced thrombocytopenia. Ann Pharmacother 2003; 37: 229–33. 160. Oberst M, Vierling P, Thielemann F. Heparinassoziierte thrombocytopenie (HAT) Typ II. Eine unterschatzte Komplikation der Thromboembolieprophylaxe mit Heparin. Chirurg 1998; 69: 198–203. 161. Olin DA, Urdaneta F, Lobato EB. Use of danaparoid during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. J Cardiothorac Vasc Anesth 2000; 14: 707–9. 162. Olivier M, de Pina J-J, Pollet L, et al. Thrombopénie induit par l’héparine: à propos d’un cas. Rev Francaise Lab 2000; 323: 75–7. 163. Ortel TL, Gockerman JP, Califf RM. Parenteral anticoagulation with the heparinoid Lomoparan (Org 10172) in patients with heparin-induced thrombocytopenia and thrombosis. Thromb Haemost 1992; 67: 292–6. [previous abstract in Blood 1989; 74 (Suppl 1): 136a Abstr 502]. 164. Pamboukian SV, Ignaszewski AP, Ross HJ. Management strategies for heparin-induced thrombocytopenia in heart transplant candidates: case report and review of literature. J Heart Lung Transplant 2000; 19: 810–4. 165. Parney IF, Steinke DE. Heparin-induced thrombocytopenia and thrombosis following subarachnoid haemorrhage. J Neurosurg 2000; 93: 136–9. 166. Perdu D, Lavaud F, Salmon V, et al. Vascular purpura induced by dalteparin. Rev Fr Allergol Immunol Clin 1999; 39: 564–6. 167. Perry SL, O,Shea SI, Ortel TL. Management of lepirudin therapy for a patient with antiphospholipid syndrome using the blood ecarin clot time and activated partial thromboplastin time. Blood Coag Fibrinolysis 2003; 14: 601–4. 168. Peters U, Egbring R, Fuchs G, et al. Aktivierung des Gerinnungs-Fibrinolyse- und Endothelzellsystems bei vier Patienten mit Heparin-induziierter Thrombozytopenie (HAT II). Haemostasiologie 1995; 15: 127–31. 169. Pfeiffer G, Eberhardt J, Hamann R. White Clot Syndrome bei heparin-induzierter thrombozytopenie Typ II mit Kreutzreaktion gegen danaparoid-Na (Orgaran®). Gefässchirurgie 2000; 5: 125–9. 170. Philipp A, Foltan M, Geitl Met al. Intervenionelle extrakorporale Lungunterstützung (ILA) mittels arterio-venosem Shunt und einem neu entwickelten Low Resistance Lung Assist Device (LAD). Kardiotechnik 2003; 1: 7–13. 171. Pineau E, Le Bret E, Folliguet T, et al. Utilisation de l’Orgaran®, heparinoïde de synthèse, lors de deux circulations extracorporelles, chez un même patient allergique a l’héparine.Arch Mal Couer 2001; 94: 144–7. 172. Piovella F, Serafini S, Barzaghi N, et al. The combined use of Iloprost with danaparoid in the surgical management of a patient with chronic thrombo-embolic pulmonary hypertension and heparin-induced thrombocytopenia. Blood 1998; 92 (Suppl 1): 124B-125B, Abstr 3509. 173. Pizzolo F, Girelli D, Olivieri O. Extensive lifethreatening thrombosis in a patient with heparin-induced thrombocytopenia and factor V Leiden mutation. Haematologica 2001; 86: 1008. 174. Plassat R, Cognet F, Ternisien C, et al. Heparin induced thrombocytopenia: Case report and literature review. Ann Readaptation Med Physique 2002; 45: 216–23. 175. Pohl C, Klockgether T, Greinacher A, et al. Neurological complications in heparin-induced thrombocytopenia. Lancet 1999; 353: 1678–9.

176. Porzelt C, Drummer B, Hoffman A. Thromboseprophylaxe in der Schwangerschaft nach Polytraumatisierung mit Splenektomie und Immobilisation bei hepariniduzierter “relativer” Thrombozytopenie Typ II. Geburtsh Frauenheilk 2002; 62: 784–6. 177. Potger KC. Use of Orgaran as an alternative to heparin during CPB. Internet slides 2004. Was available at www.perfusion.com.au. 178. Pouplard C, Forisser JF, Delahousse B, et al. Severe heparin induced thrombocytopenia with thrombosis under low molecular weight heparin treatment (tinzaparin): three case reports. Thromb Haemost 1999; 82 (Suppl): 134, Abstr 416. 179. Radke St, Schwaberg M, Storm G, et al. Das White Clot Syndrom. Zentralbl Chir 1998; 123: 573–8. 180. Ramakrishna R, Manoharan A, Kwan YL, et al. Heparin-induced thrombocytopenia: cross reactivity between standard heparin, low molecular weight heparin, dalteparin (Fragmin), and heparinoid, danaparoid (Orgaran®). B J Haematol 1995; 91: 736–8. 181. Ranze O, Eichner A, Lubenow N, et al. The use of low molecular weight heparins in heparin-induced thrombocytopenia (HIT): a cohort study. Ann Hematol 2000; 79 (Suppl 1): A 93. 182. Ranze O, Ranze P, Magnani H, et al. Heparin-induced thrombocytopenia in paediatric patients – a review of the literature and a new case treated with danaparoid sodium. Eur J Paediatr 199; 158 (Suppl 3): S130–133. 183. Rice L, Attisha WK, Drexler A, et al. Delayed onset heparin-induced thrombocytopenia. Ann Int Med 2002; 136: 210–5. 184. Robitaille D, Carrier M, Cartier R, et al. Successful management strategy for mechanical assistance and heart transplantation in patients suffering from heparin-induced thrombocytopenia Type II. J Heart Lung Transplant 2001; 20: 1237–40. 185. Roe SD, Cassidy MJD, Haynes AP. Heparin-induced thrombocytopenia (HIT) and thrombosis in a haemodialysis-dependent patient with systemic vasculitis. Nephrol Dial Transplant 1998; 14: 3226–9. 186. Rondeau M, Weber JC, Haffner C, et al. HELLP syndrome, catastrophic antiphospholipid syndrome or heparin-induced thrombocytopenia? J Autoimmun 2000; 15: A68, Abstr P147. 187. Rosel T, Druschkhy KF , Greinacher A. Complications, diagnosis and therapy of heparin-induced thrombocytopenia (HIT) Type II. Aktuelle Neurol 1999; 26: 25–30. 188. Rowlings PA, Mansberg R, Rozenberg MC, et al. The use of a low molecular weight heparinoid (Org 10172) for extracorporeal procedures in patients with heparin dependent thrombocytopenia and thrombosis. Aust NZ J Med 1991; 21: 52–4 [and as abstract Aust NZ J Med 1990; 20 (Suppl 1): 401]. 189. Salmi L, Leroy-Matheron C, LeBesnerais P, et al. Circulation extracorporelle sous danaparoïde sodique pour remplacement valvulaire au cours d’une thrombopénie induite par l’héparine de Type II. Ann Fr Anesth Reanim 2001; 20: 799–802. 190. Sauer M, Gruhn B, Fuchs D, et al. Heparin-induzierten Thrombozytopenie Typ II im Rahmen einer Hochdosis-Chemotherapie mit anschliessender Stammzellrescue. Klin Pädiatr 1998; 210: 102–5. 191. Savoia H, O’Malley C, Grigg A, et al. Haematological aspects of heparin-induced thrombocytopenia (HITS) and the incidence of cross-reactive platelet aggregation with low molecular weight heparin and Organon 10172: the Royal Melbourne Hospital experience. Abstract Austral NZ J Med 1993; 23: 120. 192. Saxon BR, Black MD, Edgell D, et al. Paediatric heparin-induced thrombocytopenia: management with danaparoid (Orgaran®). Ann Thorac Surg 1999; 68: 1076–8.

979

193. Scheffler E, Aulmann M, Remppis A, et al. Erfolgreiche Anwedung eines Heparinoids (danaparoidnatrium) wegen Heparin-induzierter Thrombozytopenie Typ II bei Aortenklappenreoperation. Z Kardiol 1995; 84: 565–8. Erratum: Z Kardiol 1996; 85: 149. 194. Schenk JF, Mösdorf S, Kroll H, et al. Prophylactic and therapeutic use of danaparoid (Orgaran®) in high risk patients – a prospective study. Ann Haematol 2000; 79 (Suppl 1): A89, Abstr P185. 195. Schiffmann H, Unterhalt M, Harms K, et al. Erfolgreiche Behandlung einer Heparin-induzierten Thrombopenie Typ II im Kindesalter mit rekombinantem Hirudin. Monatsschr Kinderheilkd 1997; 145: 606–12. 196. Schindewolf M, Mosch G, Bauersachs RM, et al. Safe anticoagulation with danaparoid in pregnancy and lactation. Thromb Haemost 200492: 211. 197. Schneider T, Heuer B, Deller A, et al. Continuous filtration with r-hirudin (Lepirudin) as anticoagulant in a patient with heparin-induced thrombocytopenia. Wien Klin Wochenschr 2000; 112: 552–5. 198. Schmal KS, Ganjoo AK, Harloff MG. Danaparoid (Org 10172) for cardiopulmonary bypass in heparin-induced thrombocytopenia: role of adjunctive plasmapheresis. J Cardiothorac VascAnesth 1997; 11: 262–3. 199. Schröder A, Scherlitzky L, Budde U, et al. Recent aspects in the diagnosis and therapy of heparin-induced thrombocytopenia type II with thrombosis or haemorrhagic complications. Zentralbl Chir 1994; 119 (Suppl 1): 151–3. 200. Serafini S, Barone M, Beltrametti C, et al. Extracorporeal circulation and heparin-induced thrombocytopenia: combined use of Iloprost and danaparoid in the surgical management of chronic thromboembolic pulmonary hypertension. Abstract. Thromb Haemost 1999; 91 (Suppl 1): S127–8. 201. Sharma S, Newman M, Gibbs N, et al. Cardiopulmonary bypass using Lomoparan: monitoring of anticoagulation using anti-Xa levels and thromboelastography. Aust NZ J Surg 1997; 67: 392–4. 202. Shlebak AA, Lennox A, Smout J, et al. Anticoagulant induced skin necrosis: association with heparin-induced thrombocytopenia and acquired protein S deficiency due to anti-phospholipid syndrome. Br J Haematol 2002; 117 (Suppl 1): 26–7, Abstr 73. 203. Smoot EC, Marx A, Weiman D, et al. Recognition, diagnosis and management of heparin-induced thrombocytopenia and thrombosis. Plastic Reconstructive Surg 1999; 103: 559–65. 204. Sodian R, Loebe M, Gorman KF, et al. Heparininduced thrombocytopenia: experiences in 12 heart surgery patients. ASAIO J 1997; 32: M430–3. 205. Sodian R, Loebe M, Hofmeister J, et al. Heparininduzierte Thrombozytopenia vom Typ II bei einem Patienten mit biventrikulärem Unterstützsungssystem. Z Herz Thorax Gefässchir 1998; 12: 140–3. 206. Stöckli TC, Walther A, Görres G, et al. Heparininduced thrombocytopenia and thrombosis. Schweiz Med Wschr 1996; 126: 483–8. 207. Strauss R, Wehler M, Mehler K, et al. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements and outcome. Crit Care Med 2002; 30: 1765–71. 208. Tardy B, Tardy-Poncet B, Viallon A, et al. Fatal danaparoid-sodium induced thrombocytopenia and arterial thromboses. Thromb Haemost 1998; 80: 530. 209. Tardy-Poncet B, Tardy B, Reynaud J, et al. Efficacy and safety of danaparoid sodium (Org 10172) in critically ill patients with heparin-associated thrombocytopenia. Chest 1999; 115: 1616–20. 210. Tardy-Poncet B, Reynaud J, Tardy B, et al. Thrombopenie induit par l’heparine: traitement par l’Org 10172. Presse Méd 1996; 25: 751–5.

Magnani, Gallus: Danaparoid treatment in HIT patients 211. Tardy-Poncet B, Reynaud J, Tardy B, et al. Efficacy and safety of Orgaran anticoagulation in patients with heparin-induced thrombocytopenia. Thromb Haemost 1995; 73: 1323, Abstr 1627. 212. Theuerkauf I, Lickfelt L, Harbrecht U, et al. Segmental hepatic vein thrombosis associated with heparin-induced thrombocytopenia II. Virchows Arch 2000; 436: 88–91. 213. Tholl U, Greinacher A, Overdick K, et al. Lifethreatening anaphylactic reaction following parathyroidectomy in a dialysis patient with heparin-induced thrombocytopenia. Nephrol Dial Transplant 1997; 12: 2750–5. 214. Tilgner J, Woydt M, Bock M, et al. Late post-operative haemorrhage in a female patient after surgery on an orbital tumor due to heparin-induced thrombocytopenia (HIT). Poster presented at the 54th Annual Meeting of the Deutsche Gesellschaft für Neurochirurgie, Saarbrücken 25.-28. May 2003. 215. Tossios P, Krian A. Heparin-induced thrombocytopenia and associated complications after routine cardiac surgery. Z Cardiol 2000; 89 (Suppl 6): 42,Abstr 8. 216. Tossios P, Atmaca N, Evagelopoulos N, et al. Experiences with danaparoid (Orgaran®) for cardiopulmonary bypass in open heart surgery: report on 5 cases. Ann Haematol 1999; 7 8(Suppl 1): A50. 217. Tran HA, Gan TE. Thrombocytopenia with idiopathic thrombocytopenic purpura (ITP) and heparininduced thrombocytopenia (HIT): double jeopardy successfully treated with cyclophosphamide and ancrod. Blood 1999; 94 (Suppl 1): 113b, Abstr 3670. 218. Vaal K, Winkler M, Rath W. Severe heparin-induced thrombocytopenia (HIT II syndrome) with sinus venosus thrombosis after female breast surgery – successful treatment with recombinant hirudin. Geburtsh Frauenheilk 1998; 58: 614–7. 219. Velten U, Mücke Th. Heparin-induzierte thrombozytopenie. Anaesthesiol Intensivmed 1996; 2: 76–80. 220. Warkentin TE, Kelton JG. Delayed onset heparin induced thrombocytopenia and thrombosis. Ann Intern Med 2001; 135: 502–6. 221. Weigel B, Laskey A, Krishnamurti L, et al. Danaparoid (Orgaran) anticoagulation of paediatric patients with heparin-induced thrombocytopenia (HIT). J Paed Haematol Oncol 2003; 21: 327, Abstr 432. 222. Wenzl ME, Leffringhausen W, Scherlitzky L. Loss of extremities caused by heparin-induced thrombocytopenia. Unfallchirurg 1996; 99: 607–11. 223. Wester JPJ, Stolk M, Geers ABM, et al. Danaparoid sodium in CAVHD in seriously ill patients with heparin-induced thrombocytopenia. Neth Med J 2000; 56: A44. 224. Wester JPJ, Haas FJLM, Biesma DH, et al. Thrombosis and haemorrhage in heparin-induced thrombocytopenia in seriously ill patients. Intensive Care Med 2004; 30: 1927–34. 225. Westphal K, Martens S, Strouhal S, et al. Heparininduced thrombocytopenia type II: peri-operative management using danaparoid in a coronary artery bypass patient with renal failure. Thorac Cardiovasc Surg 1997; 45: 318–20. 226. Weyrich P, Balletshofer B, Hoeft S, et al.Acute adrenocortical insufficiency due to heparin-induced thrombocytopenia with subsequent bilateral haemorrhagic infarction of the adrenal glands. VASA 2001; 30: 285–8. 227. Wilhelm MJ, Schmid C, Kececioglu D, et al. Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia using Org 10172. Ann Thorac Surg 1996; 61: 920–4. 228. Wilson M, Forsyth C, McGahan T, et al. Management of acute vascular graft thrombosis associated with HIT syndrome. Aust NZ J Surg 1997; 67: 302–3.

229. Wiltink EHH, Ramjankhan FZ, Haas FJLM, et al. Heparin-induced thrombocytopenia and heparin-induced thrombosis. Treatment with danaparoid and platelet-activation inhibitors. Ziekenhuisfarmacie 1996; 12: 225–7 . 230. WooYl, Allard S, Cohen H, et al. Danaparoid prophylaxis in pregnant women with heparin-induced thrombocytopenia. BJOG 2002; 109: 466–8. 231. Zimmermann-Schroeder J, Castedello Th, Bahmer FA. Heparin-induzierte Nekrosen bei dialysepflichtiger Niereninsuffizienz. Z Hautkrankheiten 1998; H+G5 (73): 273–8. 232. Zöhrer B, Zenz W, Rettenbacher A, et al. Danaparoid sodium (Orgaran®) in four children with heparininduced thrombocytopenia type II. Acta Paediatrica 2001; 90: 765–71. 233. Armager S, Ferrier-le-Bouëdec M-C, Mansard Set al. Delayed hypersensitivity skin reactions to heparins and heparinoids. Rev Fr Allerg Immunol Clin 2002; 43: 170–4. 234. Andreescu ACM, Possidente C, Hsieh M, et al. Evaluation of a pharmacy-based surveillance program for heparin-induced thrombocytopenia. Pharmacother 2000; 20: 974–80. 235. Boon DMS, Michiels JJ, Tanghe HLJ, et al. Heparin-induced thrombocytopenia with multiple cerebral infarctions simulating thrombotic thrombocytopenic purpura. Angiology 1996; 47: 11. 236. Chong BH, Mansberg R. Org 10172 in heparininduced thrombocytopenia (HIT). Aust NZ J Med 1991; 21: 949. 237. Chong BH, Jacques T. Haemofiltration/haemodialysis in patients with heparin-associated thrombocytopenia. Intensive Care Med 1991; 17: 437. 238. Deryck YL, Schepp RM, Krugten RJ van, et al. Heparinoid Org 10172 anticoagulation for cardiopulmonary by-pass: a case report. J Cardiothorac Anaesth 1990; 46 (Suppl 3): P40 . 239. Doherty DC, Ortel TL, Bruijn N de, et al. “Heparin free” cardiopulmonary bypass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardiopulmonary bypass. Anesth 1990; 73: 562–5. 240. Elalamy I, Page Y, Viallon A, et al. The diagnosis and development of heparin-induced thrombocytopenia. Clinical and biological aspects. Revue des Maladies Respiratoires 1999; 16: 961–74. 241. Eps RS van, Wester JPJ, Ruiter FE de, et al. The incidence of heparin-induced thrombocytopenia in critically ill patients with the multiple organ dysfunction syndrome. Abstract P2719 presented at the 18th ISTH congress. Thromb Haemost 2001; available on CD-ROM. 242. Eps RS van, Wester JPJ, Ruiter FE de, et al. Danaparoid sodium in continuous venovenous hemofiltration in patients with multiple organ dysfunction syndrome. Neth J Med 2000; 56: A40–41. 243. Erdlenbruch W, Stephan B, Moersdorf S, et al. The dosage of danaparoid influences significantly the increase of platelets in patients with HIT II. Ann Hematol 2001; 80 (Suppl 1): A16, Abstr 51. 244. Farag SF, Savoia H, O’Malley C, et al. Lack of in vitro cross reactivity pedicts saftey of low molecular weight heparins in heparin-induced thrombocytopenia. Aust NZ J Med 1996; 26: 276. 245. Ganzer D, Gutezeit A, Mayer G, et al. Thromboembolism prophylaxis as a cause of thromboembolic complications. An investigation into the incidence of heparin-induced thrombocytopenia (HIT) type II. Z Orthop Grenzg 1997; 90: 543–9. 246. Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-assoziierte Thrombozytopenie (HAT): Erfolgreiche Therapie von Patienten nach prospektiver Auswahl eines kompatiblen Heparinoids mit dem Heparin-

980

induzierten Plattchenaktivierungs-(HIPA)-Test. Beitr Infusionsther 1992; 30: 408–12. 247. Harbrecht UM, Pohl C, Greinacher A, et al. Neurological complications in patients with immune-mediated heparin-induced thrombocytopenia. 1999 Abstract. 248. Horellou MH, Conard J, Achkar A, et al. Treatment of thrombosis with low molecular weight heparins during 15 pregnancies in 14 women. Thromb Haemost 1997; 77 (Suppl): 733, Abstr PS-2992. 249. Kleinschmidt S, Seyfert UT. A diagnostic and therapeutic approach to heparin-associated thrombocytopenia. Clin Hemorheology 1994; 14: 137–40. 250. Mahlfield K, Bock M, Franke J, et al. The importance and incidence of heparin-induced thrombocytopenia (HIT) tpe II. A prospective study. Zentrbl Chir 2001; 126: 39–43. 251. Mahul Ph, Raynaud J, Jospe R, et al. Thrombopénie a l’héparine: utilisation d’un héparinoïde de bas poids moleculaire, l’Org 10172 (Lomoparan®) Ann Fr Anesth Reanim 1993; 12 (Suppl): R191. 252. Marshall LR, Cannell PK, Herrmann RP. Successful use of the APTT in monitoring of the heparinoid Organon 10172 in a case of HITS requiring open heart surgery. Thromb Haemost 1992; 67: 587. 253. Monagle PT, Barnes C, Newall F, et al. Twelve months experience with a paediatric thrombosis program. Blood 2001; 98: 95b, Abstr 4016. 254. Pouplard C, Amiral J, Borg Y, et al. Differences in specificity of heparin-dependent antibodies developed in heparin-induced thrombocytopenia and consequences on cross-reactivity with danaparoid sodium. B J Haematol 1997; 99: 273–80. 255. Rice L, Attisha WK, Drexler A, Francis JL. Delayed onset heparin-induced thrombocytopenia. Ann Int Med 2002; 136: 210–5. 256. Saint-Maurice O, Petrie J, Bourel P, et al. Danaparoid et chirurgie cardiaque en cas d’allergie a l’heparine. Internet publication. Danaparoid website 2002. No longer available. 257. Tardy-Poncet B. French experience in the use of Orgaran® as an alternative antithrombotic treatment for patients with heparin-induced thrombocytopenia. 16th ISTH:Abstract/Poster No PS-1825 Thromb Haemost 1997; 77 (Suppl): 447. 258. Tardy-Poncet B, Mahul P, Beraud A-M, et al. Failure of Orgaran therapy in a patient with previous heparin-induced thrombocytopenia syndrome. B J Haematol 1995; 90: 969–73. 259. Tardy-Poncet B. Efficacy and safety of Orgaran® anticoagulation in patients with heparin-induced thrombocytopenia. Thromb Haemost 1995; 73: 1627. 260. Tardy-Poncet B, Tardy B, Viallon, et al. Lower limb veins must be systematically explored in patients with isolated heparin-induced thrombocytopenia. Thromb Haemost 1999; 82 (Suppl): Abstr 804. 261. Warkentin TE. Danaparoid sodium (Orgaran®) for the treatment of heparin-induced thrombocytopenia (HIT) and thrombosis: effects on in vivo thrombin and cross-linked fibrin generation and evaluation of the clinical significance of in vitro cross-reactivity (XR) of danaparoid for HIT IgG. Blood 1996; 88 (Suppl 1): 626A, Abstr 2493. 262. Lindhoff-Last E, Kreutzenbeck H-J, Magnani HN. Treatment of 51 pregnancies with danaparoid because of heparin intolerance. Thromb Haemost 2005; 93: 63–9 . 263. Meuleman D. Danaparoid (Org 10172): Its pharmacological profile in experimental models. Haemostasis 1992; 22: 58–65. 264. Smythe MA, Warkentin TE, Stephens JL, et al. Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune

Magnani, Gallus: Danaparoid treatment in HIT patients heparin-induced thrombocytopenia. Am J Hematol 2004; 71: 50–2. 265. Bartholomew JR. Transition to an oral anticoagulant in patients with heparin-induced thrombocytopenia. Chest 2005; 127: 27–34. 266. Lubenow N, Warkentin TE, Greinacher A, et al. A systematic evaluation of treatment outcomes for heparin-induced thrombocytopenia in patients receiving danaparoid, ancrod and/or coumarin explains the rapid shift in clinical practice during the 1990s. Thromb Res 2005; 117: 507-15. 267. Greinacher A, Warkentin TE. Treatment of heparin-induced thrombocytopenia: an overview. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 335–70. 268. Shalansky SJ, Verma AK, Levine M. Factors to consider before discontinuing heparin in patients who develop thrombocytopenia. Pharmacotherapy 1999; 19: 1011–2. 269. Warkentin TE, Greinacher A. Laboratory testing for HIT. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 313–70. 270. Lubenov N, Eichler, Albrecht D, et al. Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia: report of four cases and review of literature. Thromb Res 2000; 100: 115–25. 271. Anon. Early awareness key to successful management of heparin-induced thrombocytopenia (HIT). Drug Ther Perspect 2001; 17: 8–12. 272. Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost 1998; 79: 1–7. 273. Kiefel V. Differential diagnosis of acute thrombocytopenia. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 25–52. 274. Warkentin TE. Pseudoheparin-induced thrombocytopenia. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 313–34. 275. Griffiths E, Dzik WH. Assays for heparin-induced thrombocytopenia. Transfusion Med 1997; 7: 1–11. 276. Warkentin TE, Heddle NM. Laboratory diagnosis of immune heparin-induced thrombocytopenia. Current Hematology Reports 2003; 2: 148–57. 277. Danhof M, de Boer A, Magnani HN, et al. Pharmacokinetic considerations on Orgaran (Org 10172) therapy. Haemost 1992; 22: 73–84. 278. Carrier M, Robitaille D, Perrault LP, et al. Heparin versus danaparoid in off-pump coronary by-pass graft-

ing: results of a prospective randomised clinical trial. J Thorac Cardiovasc Surg 2003; 125: 325–9. 279. Warkentin TE, Dunn GL, Cybulsky IJ. Off-pump coronary artery bypass grafting for acute heparin-induced thrombocytopenia. Ann Thorac Surg 2001; 72: 1730–2. 280. Greinacher A. Lepirudin in HIT treatment. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 397–436. 281. Lewis B, Hursting MJ. Argatroban therapy in heparin-induced thrombocytopenia. In: Heparin-Induced thrombocytopenia, 3rd Edition. Ed. Warkentin TE, Greinacher A, Marcel Dekker Inc. 2004: 437–74. 282. Makhoul RG, Greenberg CS, McCann RL. Heparin associated thrombocytopenia and thrombosis: a serious problem and potential solution. J Vasc Surg 1999; 4: 522–8. 283. Eichler P, Budde U, Haas S, et al. First workshop for the detection of heparin-induced antibodies: Validation of the heparin-induced platelet activation assay (HIPA) in comparison with a PF4/heparin ELISA. Thromb Haemost 1999; 81: 625–9. 284. Blockmans D, Bounameux H, Vermylen J, et al. 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. 285. Elalamy I, Lecrubier C, Potevin, et al. Absence of in-vitro cross reaction of pentasaccharide with plasma heparin-dependent factor of twenty five patients with heparin-associated thrombocytopenia. Thromb Haemost 1995; 74: 1384–85. 286. Harbrecht U, Unkrig CJ. Heparin-induced thrombocytopenia Type II: platelet aggregation studies with low molecular weight heparin and heparinoid Org 10172. Thromb Haemost 1991; 65: 1302. 287. Kikta MJ, Keller MP, Humphrey PW, et al. Can low molecular weight heparins and heparinoids be safely given to patients with heparin-induced thrombocytopenia syndrome? Surgery 1993; 114: 705–10. 288. Kleinschmidt S, Seyfert UT. Heparin-associated thrombocytopenia (HAT) – still a diagnostic and therapeutic problem in clinical practice. Angiology 1995; 46: 37–44. 289. Koster A, Kuppe H, Hetzer R, et al. Emergent cardiopulmonary bypass in five patients with heparin induced thrombocytopenia Type II employing recombinant hirudin. Anaesthesiology 1998; 89: 777–80. 290. Kroll H, Jonas T, Kreiling S. Immunologic analysis of 4741 patients with clinically suspected heparin-

981

induced thrombocytopenia. Ann Hematol 2000; 79 (Suppl 1): A88, Abstr 182. 291. Schmidt S, Ludtke-Handjery A, Lottermoser KH. Die Heparin-assozierte Thrombozytopenie als Problem der Heparintherapie. Chirurg 1993; 64: 715–9. 292. Tomer A, Masalunga C, Abshire TC. Determination of heparin-induced thrombocytopenia: a rapid flow cytometric assay for direct determination of antibody mediated platelet activation. Am J Hematol 1999; 61: 53–61. 293. Vun CM, Evans S, Chong BH. Cross-reactivity study of low molecular weight heparins and heparinoid in heparin-induced thrombocytopenia. Thromb Res 1996; 81: 525–32. 294. Walenga J, Silber I, Koza M, et al. Lack of heparin induced thrombocytopenia response with the use of the new antithrombotic agents. Blood 1991; 78 (Suppl 1): Abstr 569. 295. Warkentin TE. Heparin-induced thrombocytopenia, Part 2: clinical course and treatment. J Crit Illness 2002; 17: 215–21. 296. Figarella I, Barbaud A, Lecompte T, et al. Réaction cutanée d’hypersensibilité retardée avec polysensibilisation aux héparines et héparinoïdes. Ann Dermatol Venereol 2001; 128: 25–30. 297. Grassegger A, Fritsch P, Reider N. Delayed-type hypersensitivity and cross-reactivity to heparins and heparinoids: a prospective study. Dermatol Surg 2001; 27: 47–52. 298. Harenberg J, Huhle G, Wang L, et al. Association of heparin-induced skin lesions, intracutaneous tests and heparin-induced IgG. Allergy 1999; 54: 473–7. 299. Koch P, Müßinger, Rupp-John C, Uhl K. Delayedtype hypersensitivity skin reactions caused by subcutaneous unfractionated and low molecular weight heparins: tolerance of a new recombinant hirudin. J Am Acad Dermatol 2000; 42: 612–9. 300. Wutschert R, Piletta P, Bounameaux H. Adverse skin reactions to low molecular weight heparins. Drug Safety 1999; 20: 515–25. 301. Nicolie B, Bonneau J-C, Le Sellin J, et al. Hypersensibilite retardee aux heparines et heparinoides. Allergie et Immunologie 2002; 34: 47–50. 302. Boehncke WH, Weber L, Gall H. Toleranz gegenüber intravenöser Applikation von Heparin und Heparinoid bei einer Patientin mit Typ-IV Allergie auf Heparine und Heparinoide. Allergologie 1996; 19: 95. 303. Drew PJ, Smith MJ, Milling MAP. Heparin-induced skin necrosis and low molecular weight heparins. Ann R C Surg Engl 1999; 81: 266–9.