Sudden onset of EDTA-dependent pseudothrombocytopenia after therapy with the glycoprotein IIb/IIIa antagonist c7E3 Fab

Abstract

The development of thrombocytopenia following exposure to the platelet glycoprotein (GP) IIb/ IIIa receptor antagonist abciximab (c7E3 Fab, ReoPro) is associated with adverse clinical outcome and excessive bleeding. Pseudothrombocytopenia is an important differential diagnosis in sudden onset of thrombocytopenia in a patient treated with c7E3 Fab. We report on a case of documented sudden onset of EDTA-dependent pseudothrombocytopenia in a 63-year-old woman who was admitted for emergency coronary intervention. Four hours after bolus administration of c7E3 Fab, the platelet concentration in EDTA-anticoagulated blood decreased from 385 x 10(9)/l to 119 x 10(9)/l, and it showed a further decrease to 57 x 10(9)/l at the end of a 12-h infusion. Despite no warnings or abnormalities of the automated cell counter, platelet aggregates were observed by microscopic evaluation of the blood smear. Repeated platelet counts in citrate-anticoagulated samples revealed platelet concentrations within the reference range. EDTA-dependent pseudothrombocytopenia due to therapy with c7E3 Fab is an important differential diagnosis that needs to be excluded rapidly from other causes of thrombocytopenia to avoid unnecessary further examinations, discontinuation of therapy, or even initiation of inappropriate therapy.

EDTA-dependent pseudothrombocytopenia in a patient with the prediagnosis of idiopathic thrombocytopenic purpura

“…Psödotrombositopeniyi saptamak için farklı yöntem-ler bulunmuştur. EDTA yerine diğer antikoagülanların (sodyum sitrat, oksalat ve heparin) kullanılması [12,13], EDTA ile antikoagüle edilmiş kanın 37 0 C'ye getirilerek incelenmesi [1,4], mikroskop altında trombosit kü-meleşmesinin saptanması [5], mekanizması henüz bilinmemesine rağmen kanamisin eklenmiş kan örnekleri-nin kullanılması bu yöntemlerdendir [8]. Çalışmamızda psödotrombositopeniyi saptamak amacıyla EDTA yerine antikoagülan olarak ilk aşamada sitratı seçtik.…”

“…ITP'de gözlenen trombosit büyüklüğündeki artış, myeloproliferatif bozukluklarda, megaloblastik anemi, Bernard-Soulier sendromu ve May-Heggelin anomalisinde de görülebilir (15). Psödotrombositopeni fenomeninde ise trombositler normal büyüklük ve morfolojiye sahiptir ancak yaygın kümeleşme gösterirler (2,5). Olgumuzda ise EDTA'lı örneğe kıyasla oda sıcaklığındaki sitrat- lı ve KN-EDTA'lı örneklerden yapılan yaymalarda trombosit kümeleşmesi yaygın olmadığı gibi trombosit sayısı ve büyüklükleri de normaldi.…”

“…Düşük sıcaklık ve EDTA'nın kalsiyum iyonlarına bağlanırken oluşturduğu kombine etki, normalde saklı olan ve trombosit yüzeyinde bulunan glikoprotein IIb/IIIa molekülünü etkileyerek glikoprotein IIb epitopunu açığa çıkarır. Eğer kişide bu epitopa karşı otoantikor mevcutsa, antikor trombositlere bağlanarak trombositlerin kümeleşmesine neden olur [3][4][5]. Bu tedavi gerektirmeyen EDTA'ya bağlı psödotrombositopeni (EDTA-PTP) fenomeni, çoğu zaman gerçek trombositopenilerle karıştırılır.…”

Pseudothrombocytopenia

“…Agglutination specifi c for these antigens blocks them and causes lack of thrombocyte agglutination under the eff ect of EDTA. On the other hand, blocking GPIb does not lead to an inhibition of thrombocyte agglutination under the eff ect of EDTA [10].…”

Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia in a patient with systemic lupus erythematosus and lupus nephritis

“…The disorder is caused by antibodies that recognize platelet antigens modified or exposed to the combined action of ethylenediaminetetraacetic acid (EDTA) and low temperature on platelet membrane glycoproteins (5). Methods for detecting pseudothrombocytopenia include the replacement of anticoagulants (sodium citrate and heparin) with EDTA and the determination of platelet aggregation through a microscope (6). Methods for detecting pseudothrombocytopenia also include the replacement of anticoagulants (sodium citrate and heparin) with EDTA to the other way, use the EDTA first as that was the culprit and the pseudothrombocytopenia was revealed by switching anticoagulants.…”