Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia in complex cardiac surgery | |
DOI: 10.5606/e-cvsi.2017.623 | |
Burak Onan, Barış Timur, Ersin Kadiroğulları, Korhan Erkanlı | |
Department of Cardiovascular Surgery, İstanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, İstanbul, Turkey | |
Keywords: Cardiac surgery; ethylenediaminetetraacetic acid-dependent; ethylenediaminetetraacetic acid; pseudothrombocytopenia; pseudothrombocytopenia | |
Pseudothrombocytopenia is an unusual hematological disorder, which develops in response to ethylenediaminetetraacetic acid-dependent
anti-platelet autoantibodies in blood, leading to platelet clumping. It is only an in vitro phenomenon, which presents with low platelet
counts in routine hematology analysis. The definitive diagnosis should be established to avoid a delay in surgery and unnecessary blood
transfusion in patients undergoing cardiovascular surgery. Herein, we present a 51-year-old female case with ethylenediaminetetraacetic
acid-dependent pseudothrombocytopenia, who underwent a successful aortic root and valve surgery, and discuss perioperative management
of this rare disorder. |
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Pseudothrombocytopenia is a rare hematological
disorder of platelet clumping related to
ethylenediaminetetraacetic acid (EDTA)-dependent
antiplatelet autoantibodies in blood.[1-4] The EDTA
is a safe anticoagulant for a complete blood count
analysis. However, this agent may induce the clumping,
which causes the automatic hematology analyzers
to undercount platelets, thereby, resulting in low
platelet counts. Pseudothrombocytopenia is only an
in vitro effect, which does not cause any hemostatic
complications, as all platelet functions and coagulation
tests are normal.[5] It can be seen in some patients
with autoimmune diseases, malignancies, chronic
liver diseases, viral infections, and cardiovascular
diseases. In addition, pregnant women and healthy
individuals may rarely present with this disorder.[5]
The diagnosis of pseudothrombocytopenia is of unique
clinical importance to avoid a delay in surgery and
unnecessary blood transfusion in patients undergoing
cardiac surgery. Although EDTA-dependent pseudothrombocytopenia has been previously described in patients undergoing cardiac surgery,[2-4] its clinical features and management approaches still remain controversial for cardiac surgeons. Herein, we present a case of pseudothrombocytopenia who underwent aortic root replacement, mitral valve replacement, and tricuspid valve repair and discuss perioperative management of this entity. |
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CASE PRESANTATION
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A 51-year-old female was referred to our hospital with
progressive dyspnea due to valvular heart disease.
Her medical history revealed chronic renal failure
and hypertension. She was also on medical treatment
for hypertension with angiotensin-receptor blockers.
On admission, her vital signs were stable. Physical
examination revealed aortic, mitral, and tricuspid
diastolic murmur. In the biochemical analysis, low
platelet counts (65,000/mm3) were observed. There
was no skin lesion such as petechiae, ecchymosis, or
purpura. Other than thrombocytopenia, biochemical
and serological test results were normal without any
indicator of an infection, inflammatory disease or
coagulation disorder. Electrocardiography revealed
sinus rhythm with a left-axis deviation. A chest X-ray
showed cardiomegaly with enlarged left chambers.
Echocardiography revealed an ejection fraction of 45% with a severe aortic and mitral valve regurgitation and
moderate tricuspid valve regurgitation. Pulmonary
artery pressure was 40 mmHg. It also showed enlarged
left cardiac chambers, mild pericardial effusion, and an
aneurysm of the ascending aorta. Thoracic computed
tomography revealed an aortic annulus of 30 mm, sinus
of Valsalva of 43 mm, sinotubular junction of 36 mm,
and ascending aorta of 51 mm in size. Coronary
angiography demonstrated no abnormality of coronary
arteries. The patient was decided to undergo the
Bentall procedure with mitral valve replacement
and tricuspid valvuloplasty. Preoperatively, she
was referred to a hematology consultant. EDTAdependent
pseudothrombocytopenia was diagnosed
with a peripheral blood smear which showed platelet
clumping (Figure 1). Clumping was not observed
after analysis of heparinized blood sample. Surgery
was decided based on the discretion of the consultant
hematologist. The operation was performed with a median sternotomy and systemic heparinization. Cardiopulmonary bypass was initiated through the cannulation of the ascending aorta and both vena cava. Cardiac arrest was established with antegrade infusion of isothermic blood cardioplegia through the coronary ostia. First, right atriotomy incision was performed and, using transseptal incision, the mitral valve was explored. It was degenerated and replaced with a No. 29 bileaflet mechanical valve, preserving the posterior mitral leaflet. Then, the Bentall procedure with a No. 21 mechanical aortic valve conduit was performed. Finally, the tricuspid valve annuloplasty was made using a No. 29 flexible annuloplasty ring. The valve showed a good coaptation on saline test. The operation was completed uneventfully. Cardiopulmonary bypass and aortic cross-clamp times were 169 and 137 min, respectively. She was transferred to the ward on postoperative Day 1 with a platelet count of 74,000/m3. No platelet suspension was delivered postoperatively. The patient was discharged home with a favorable outcome on postoperative Day 6. The platelet count ranged between 65,000 and 87,000/mm3. Routine anticoagulation was delivered, including early delivery of low-molecular-weight heparin and warfarin with an international normalized ratio of ranging between 2.5 and 3.5. At four months of follow-up, she is still disease-free. |
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Acquired platelet disorders are mainly classified into
disorders of the platelet count and function.[1] The
etiology of low platelet count includes decreased
production by bone marrow and increased peripheral
destruction due to immunological causes, nonimmunological
disorders, hemodilution, and
pseudothrombocytopenia. The prevalence of EDTAdependent
pseudothrombocytopenia is reported to be
between 0.1% and 2% among hospitalized patients and
up to 17% in patients with isolated thrombocytopenia.[3,5]
The EDTA is an anticoagulant, which is frequently
used for hematological tests, and may induce platelet
clumping. However, some other anticoagulants such
as heparin, oxalate, hirudin, citrate, or abciximab may
also cause pseudothrombocytopenia, although their
actual incidence is still unclear.[5] The underlying mechanism of platelet clumping in pseudothrombocytopenia includes an immunological process which was first described by Shreiner and Bell in 1973.[6] The authors proved that EDTA caused a new type of platelet agglutinin, which was active at 37 °C, as well as at room temperature. The EDTA-dependent antiplatelet antibodies recognize and activate different receptors, such as glycoprotein IIb-IIIa and thrombospondin, resulting in platelet clumping in the in vitro setting. Previously, Bizzaro[1] reported antiplatelet antibodies in 83% of the patients with pseudothrombocytopenia.[1] These antibodies were majorly immunoglobulin (Ig) M or IgG. In addition, a small number of patients had an IgA class.[1] Although platelet clumping occurs during hematological tests, the number and function of the platelets can be normal in patients with pseudothrombocytopenia in the in vitro setting.[1] Previous reports also showed that low platelet counts were not associated with an increased risk of bleeding in the perioperative period of cardiac surgery.[2-5] Although the cardiac surgical practice is itself associated with hemorrhagic complications, EDTA-dependent pseudothrombocytopenia presents with a benign course.[2-4] Preoperatively, patients usually have low platelet counts in the routine blood tests. Due to platelet clumping, conventional automated hematology analyzers count each clump as one and do not show the actual number of platelets. Therefore, the visual assessment of blood smears for clumping is considered as the gold standard for the diagnosis of this phenomenon.[1-5] Unawareness of this entity may lead to a delay in cardiac procedures or unnecessary transfusion in the perioperative period. These may, eventually, lead to severe complications, particularly in high-risk patients with a critical coronary or valve disease. In the literature, pseudothrombocytopenia in cardiovascular operations has been described in few reports; however, it is still an unusual entity for cardiac surgeons.[2-4] The first report by Dalamangas et al.[3] described an uneventful coronary revascularization and aortic valve replacement using cardiopulmonary bypass. Then, Wilkes et al.[2] presented a patient with anticoagulant-induced pseudothrombocytopenia who underwent a successful coronary artery bypass grafting. The authors confirmed the low platelet count and clumping with microscopic examination, and concluded that clumping was associated with both EDTA and citrate on hematological analysis in the postoperative period. On the other hand, Nair et al.[4] reported that EDTA-dependent pseudothrombocytopenia could be easily diagnosed by repeating platelet counts in citrate and heparin-anticoagulated blood samples. These reports confirm that any type of anticoagulant can be associated with clumping. To the best of our knowledge, our case is the first report of a complex cardiac surgery with a prolonged cardiopulmonary bypass time in pseudothrombocytopenia. The diagnostic approaches in such cases include blood smears which are simple and valuable tests to show an abnormality of clumping or hemostasis. Laboratory tests such as thromboelastography, which shows specifically the function of platelets, can be also used to reveal an abnormality of coagulation related to platelets. It is a simple and rapid tool for the diagnosis of hemostatic disorders; however, the availability of this tool is limited. Beyond the diagnostic tests, clinical experience is also important for hemostasis in complex and prolonged cases. In our case, if the duration of the procedure prolonged, which means coagulation can be affected from the cardiopulmonary bypass time, we could use platelet suspensions after weaning from cardiopulmonary bypass. Indeed, there is no known drawback of using platelets in prolonged and complex cardiac surgery procedures. In conclusion, ethylenediaminetetraacetic aciddependent pseudothrombocytopenia is a rare disorder of platelet clumping during hematological testing. It is a benign phenomenon and does not pose an increased risk for perioperative bleeding. The definitive diagnosis of pseudothrombocytopenia prevents unnecessary testing for thrombocytopenia, a delay in surgery, and unnecessary platelet transfusions.
Declaration of conflicting interests
Funding |
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1) Bizzaro N. EDTA-dependent pseudothrombocytopenia: a
clinical and epidemiological study of 112 cases, with 10-year
follow-up. Am J Hematol 1995;50:103-9.
2) Wilkes NJ, Smith NA, Mallett SV. Anticoagulant-induced
pseudothrombocytopenia in a patient presenting for
coronary artery bypass grafting. Br J Anaesth 2000;84:640-2.
3) Dalamangas LC, Slaughter TF. Ethylenediaminetetraacetic
acid-dependent pseudothrombocytopenia in a cardiac
surgical patient. Anesth Analg 1998;86:1210-1.
4) Nair SK, Shah R, Petko M, Keogh BE.
Pseudothrombocytopenia in cardiac surgical practice.
Interact Cardiovasc Thorac Surg 2007;6:565-6.
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