Institute of Cardiovascular Diseases
Clinical Centre of Serbia
Belgrade
E-mail address: drantoni{at}yubc.net
Institute of Haematology
Clinical Centre of Serbia
Belgrade
Institute of Cardiovascular Diseases
Clinical Centre of Serbia
Belgrade
Institute of Cardiovascular Diseases
Clinical Centre of Serbia
Belgrade
Institute of Cardiovascular Diseases
Dedinje
Belgrade
Institute of Cardiovascular Diseases
Clinical Centre of Serbia
Belgrade
Thoroughly analysing directions of the still valid Guidelines on diagnosis and management of acute pulmonary embolism (PE) published by European Heart Journal in 2000 throughout the management of our patients with PE caused by heparin-induced thrombocytopaenia Type II (HIT II),1 we have noticed that its section Epidemiology and predisposing factors completely fails to give any attention to HIT II as the possible risk factor for venous thrombo-embolism, whereas this issue received little attention under the section Treatment of PE. Apart from the introduction of immediate active non-heparin anticoagulants upon heparin therapy discontinuation, the latter section also advises the use of r-hirudin derivatives in patients with HIT associated with a new thrombotic episode or aggravated PE. However, the same applies to the danaparoid sodium administration which is suggested in low doses of no more than 2x750 IU subcutaneously, today considered as preventive doses, while the intravenous route remains vague as to both the specific group of patients to receive it and its dosage.1
We have adopted a more recent attitude that a therapeutic danaparoid regimen initiated with a loading dose of 2250 units followed by the stated maintenance dose of 400 units/h and later 300 units/h over the first 7 h further continued with 200 units/h is considerably safer than low preventive doses in HIT with thromboses.24 The given full therapeutic doses are more than 4.5 times higher during the first therapeutic day and about three times higher than the preventive ones a day after the drug initiation.3,4
Our attitude that the preventive doses, nowadays held to be underdosed even in cases of HIT without thrombosis, so-called isolated HIT, may lead to the prolongation of natural course of disease is further supported by a latter-day retrospective study showing that danaparoid sodium for isolated HIT received in low prophylactic doses is associated with a high failure rate compared with patients received lepirudin in APTT-adjusted doses. This speaks in favour of the use of therapeutic-dose danaparoid in both isolated HIT and HIT with PE.3
Our recent clinical practice has registered nine successfully treated patients diagnosed with PE caused by HIT II. Initial danaparoid sodium (four patients) or lepirudin (three patients) treatment was successful in seven patients. The remaining two fell into the category of full therapeutic dose-danaparoid sodium resistant cases. One of these patients responded positively only upon lepirudin introduction, whereas in the other patient, no effect was produced even by therapeutic lepirudin doses where the remission was achieved only after plasmapheresis. Thus, it has not escaped our notice that the management of patients resistant to initial non-heparin anticoagulants was absolutely neglected, not only in the Guidelines themselves but also in other principal reference sources, though such cases account for a considerable proportion of HIT II patients treated with danaparoid sodium or lepirudin2 as non-heparin anticoagulants of similar efficacy (9.4% thrombosis rate with danaparoid vs. 7.9% thrombosis rate with lepirudin).3 Administration of new anticoagulants of bivaluridin and fondaparinux type may even have certain advantages over the standard alternative non-heparin anticoagulants.3
Hope remains that new guidelines for the diagnosis and treatment of PE will take into account the complexity of both HIT II patients and individualized treatment demands dependent on their specific state of haemostasis, possible accompanying diseases, and the patient's resistance to initial therapy, with special reference to the application of adjunctive measures, of which plasmapheresis has a proved clinical effect.2,5,6
References
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