Homem de 61 anos de idade, com diagnóstico de síndrome mielodisplásica e angina instável foi submetido a angiografia coronariana e implante de stent. O hemograma revelou 40.000/mm³ plaquetas. A angiografia coronariana, precedida por transfusão de plaquetas, revelou obstrução de 80% no óstio da artéria coronariana direita (ACD). Após o uso de clopidogrel 75mg, o paciente foi submetido à nova transfusão de plaquetas e a implante de stent LEKTON 3,0x10mm na lesão da ACD. Não ocorreram sangramentos após as retiradas dos introdutores. Após seis meses, o teste de esforço foi positivo e nova angiografia, sob as mesmas condições anteriores, mostrou reestenose intra-stent. Esse relato sugere que o implante de stent coronariano em pacientes com plaquetopenia é seguro, contanto que se realize a transfusão profilática de plaquetas, embora em longo prazo possa haver reestenose.
Hospital do Servidor Público Estadual de São Paulo, São Paulo, SP
Homem de 61 anos de idade, com diagnóstico de síndrome mielodisplásica e angina instável foi submetido a angiografia coronariana e implante de
As síndromes mielodisplásicas são um grupo heterogêneo de desordens da medula óssea caracterizado por anormalidades morfológicas das séries eritróide, granulocítica e megacariocítica com medula óssea hipercelular¹. Quando é acometida a série megacariocítica, a tendência hemorrágica se torna um importante agravante clínico. A associação de doença coronariana e trombocitopenia por síndrome mielodisplásica é um desafio para a cardiologia intervencionista na qual as intervenções coronarianas percutâneas requerem tanto evitar a trombose intracoronária com o uso de drogas antiagregantes plaquetárias, quanto evitar sangramentos após o procedimento.
Homem de 61 anos, aposentado, foi admitido com história de dor precordial opressiva, aos grandes esforços, com início há 8 meses e progressão para os pequenos esforços há 1 mês. Apresentava como fator de risco para doença coronariana, somente hipertensão arterial sistêmica. Fazia uso irregular de ácido acetilsalicílico (AAS) 200mg, propranolol 40 mg de 12 em 12 horas, omeprazol 20 mg, ácido fólico 5 mg e complexo B.
Há um ano apresentou hemorragia gengival espontânea e petéquias. O hemograma na ocasião mostrou 20.000 plaquetas por mm³. Foi submetido a mielograma e a exame imunohistoquímico da medula óssea que confirmaram o diagnóstico de síndrome mielodisplásica das séries granulocítica e megacariocítica, com série eritróide preservada. Naquela ocasião foi medicado com ácido fólico, piridoxina e cianocobalamina. A contagem de plaquetas manteve-se em torno de 40.000/mm³ e não ocorreram outros eventos hemorrágicos.
Ao exame físico, apresentava hipoplasia (focomelia) dos membros superiores, pressão arterial de 180/110 mmHg e freqüência cardíaca de 96 bpm. A ausculta cardiopulmonar era normal.
O eletrocardiograma de repouso mostrou ritmo sinusal com alterações inespecíficas da repolarização ventricular na parede inferior e, na vigência de dor precordial, infradesnivelamento do segmento ST e inversão da onda T (tipo
O paciente foi submetido à angiografia coronariana, após duas horas da transfusão de 10 unidades de plaquetas. O exame foi realizado por punção da artéria femoral direita (AFD), técnica de Judkins e utilizaram-se introdutor e cateteres 6F. Imediatamente após o procedimento foi retirado o introdutor da AFD e realizada compressão local por 20 minutos. Não ocorreu sangramento ou hematoma após a compressão. O exame revelou lesão obstrutiva com porcentual de estenose de 80% no óstio da artéria coronária direita (ACD) cujo diâmetro de referência foi 3,05 mm (
Após seis dias do uso de clopidrogel 75 mg ao dia e duas horas de nova transfusão de 10 unidades de plaquetas, o paciente foi submetido a implante direto de
A evolução hospitalar ocorreu sem intercorrências. Após sete dias do implante de
Evoluiu assintomático e aos seis meses pós-implante foi realizado teste de esforço que mostrou infradesnivelamento de ST de 2 mm nas derivações inferiores. Submeteu-se a novo cateterismo cardíaco por punção da AFD após 2 horas da transfusão de 8 unidades de plaquetas. Foi observada lesão obstrutiva com porcentual de estenose de 70% intra-
A associação de trombocitopenia por síndrome mielodisplásica e doença coronariana é rara, e são escassas as publicações do tratamento pela intervenção coronariana percutânea das lesões obstrutivas em pacientes com plaquetopenia. Foram relatados, na literatura médica, dois casos de pacientes com púrpura trombocitopênica idiopática submetidos a angioplastia transluminal coronariana para tratamento de infarto agudo do miocárdio2,3, sendo que em um deles foi realizado o implante de
O paciente apresentava, além da síndrome mielodisplásica, focomelia dos membros superiores, anomalia congênita em que ocorre a ausência dos rádios. Foi descrita a associação de focomelia com trombocitopenia e diminuição dos megacariócitos no mielograma: a síndrome TAR (
A plaquetopenia, baseada na contagem absoluta de plaquetas, pode ser dividida nas seguintes categorias: leve (<150.000/mm³), moderada (50 – 100.000 /mm³), acentuada (20 – 50.000/mm³) e profunda (< 20.000/mm³). A não linearidade do tempo de sangramento associada à plaquetopenia de diferente etiologia e o valor definido foi demonstrada por Harker. Isto resulta em diferenças na contagem absoluta de plaquetas nos guias médicos na indicação da transfusão de plaquetas em pacientes com plaquetopenia de diferentes etiologias6. De acordo com o America's Blood Centers, a transfusão de plaquetas deve ser administrada profilaticamente em pacientes com contagem de plaquetas menor que 50.000/mm³ que vão submeter-se à cirurgia ou a procedimento invasivo onde o campo operatório pode ser visibilizado ou pressão externa pode ser utilizada para manter a hemostasia7.
No presente caso, a contagem de plaquetas foi 40.000/mm³ e foi realizada transfusão de 10 unidades de plaquetas 2 horas antes dos procedimentos, a fim de elevar o número de plaquetas acima de 50.000/mm³. Esta conduta mostrou-se segura tanto para a angiografia coronariana quanto para o implante de
O uso de heparina na dose de 100 UI por kg durante o procedimento também se mostrou segura, sendo o introdutor retirado da artéria femoral 4 horas após o procedimento, não ocorrendo sangramento ou formação de hematoma.
É recomendado o uso de introdutores e cateteres de pequeno diâmetro para facilitar a hemostasia pós-procedimento. No presente caso foi utilizado material 6F por ser o menor diâmetro disponível e via punção da artéria femoral por ser a técnica utilizada pela nossa equipe de hemodinâmica. A via radial é uma via alternativa para os pacientes com plaquetopenia, não utilizada neste caso por não ser rotina em nossa instituição8.
Os estudos clínicos mostram uma maior taxa de reestenose em pacientes com localização aorta-ostial pós-implante de
A fissura ou ruptura da placa aterosclerótica constitui o mecanismo fisiopatológico mais importante da angina instável. Após a rotura, a subseqüente adesão e agregação de plaquetas e à formação de trombo, assim como a hemorragia e o edema dentro da placa contribuem para o agravamento da estenose10. Este paciente apesar de apresentar plaquetopenia, evoluiu com quadro de angina instável progressiva, o que nos leva a supor que apesar do número reduzido de plaquetas, a função plaquetária permaneceu normal, o que justifica o uso de antiagregante plaquetário como prevenção da trombose aguda ou subaguda pós-implante de
A plaquetopenia, mantida em torno de 20.000/mm³, não conferiu proteção contra a reestenose aos seis meses pós-implante do
A descrição do caso sugere que a angiografia e a intervenção coronariana percutânea em pacientes com plaquetopenia são seguras, desde que se realize transfusão de plaquetas profilática duas horas antes dos procedimentos, embora em longo prazo possa haver reestenose.
George César Ximenes Meireles Rua Sena Madureira, 1265/102 04021-051 – São Paulo, SP E-mail:
Recebido em 07/12/04; revisado recebido em 24/06/04; aceito em 24/02/06.
Sixty-one-year-old male patient with diagnosis of myelodysplastic syndrome and unstable angina was submitted to coronary angiography and implant of stent. His Blood vell count revealed 40,000 platelets/mm³. Coronary angiography with previous platelet transfusion showed obstruction of 80% of the right coronary artery (RCA). Following the administration of clopidogrel, the patient was submitted to another platelet transfusion and stent implantation in the RCA lesion. No bleeding was observed after the introducers removal. After 6 months, treadmill test was positive and new coronary aniography, in the same conditions, showed in-stent restenosis. This case report suggests that coronary stent implantation in patients with thrombocytopenia is a safe procedure, provided that prophylactic platelet transfusion is performed, although late restenosis may occur.
Hospital do Servidor Público Estadual de São Paulo, São Paulo, SP, Brazil
Sixty-one-year-old male patient with diagnosis of myelodysplastic syndrome and unstable angina was submitted to coronary angiography and implant of stent. His Blood vell count revealed 40,000 platelets/mm³. Coronary angiography with previous platelet transfusion showed obstruction of 80% of the right coronary artery (RCA). Following the administration of clopidogrel, the patient was submitted to another platelet transfusion and stent implantation in the RCA lesion. No bleeding was observed after the introducers removal. After 6 months, treadmill teste was positive and new coronary aniography, in the same conditions, showed in-stent restenosis. This case report suggests that coronary stent implantation in patients with thrombocytopenia is a safe procedure, provided that prophylactic platelet transfusion is performed, although late restenosis may occur.
Myelodysplastic syndromes are a heterogeneous cluster of bone marrow disorders characterized by morphological abnormalities of the erythroid, granulocytic, and megakaryocytic series and a hypercellular bone marrow1. When the megakaryocytic series is affected, the hemorrhagic tendency is a major aggravating factor. The association of coronary disease and thrombocytopenia due to myelodysplastic syndrome presents a challenge to interventional cardiology, because percutaneous coronary interventions require preventing both intracoronary thrombosis with antiplatelet agents and bleeding after the procedure.
A sixty-one-year-old retired man was admitted to the hospital with a history of pressure-like precordial pain for eight months. First brought on by heavy exertion, one month before admission it started being triggered by mild exertion also. The patient's only risk factor for coronary disease was systemic arterial hypertension. He was taking acetylsalicylic acid (ASA) 200 mg irregularly, propranolol 40 mg every 12 hours and omeprazol 20 mg, folic acid 5 mg, and vitamin B complex daily.
One year previously, he had developed spontaneous gum bleeding and petechiae. On that occasion, his platelet count was 20,000/mm³. Myelogram and bone marrow immunohistochemical studies confirmed the diagnosis of myelodysplastic syndrome involving the granulocytic and megakaryocytic series, with normal erythroid series. The patient was then medicated with folic acid, pyridoxine, and cyanocobalamin. His platelet count remained around 40,000/mm³, and no further bleeding events occurred.
Physical examination showed upper limb hypoplasia (phocomelia), blood pressure of 180/110 mmHg, and heart rate of 96 bpm. Cardiopulmonary auscultation was normal. Resting electrocardiogram showed sinus rhythm with nonspecific ventricular repolarization changes in the inferior wall. During precordial pain episodes, ST-segment depression and T-wave inversion (plus-minus) were observed in the same region. Chest radiography revealed cardiothoracic index of 0.5 and normal pleuropulmonary fields. Transthoracic echocardiogram (TTE) showed moderate left ventricular dysfunction due to hypokinesia of inferior, lateral, and posterior walls, with ejection fraction of 0.40. Results of laboratory tests were as follows: platelet count of 40,000/mm³, leukocyte count of 1,850/mm³, and hemoglobin level of 13.2 g/dl. Clotting profile was within normal limits, with INR (international normalized ratio) 1.09 (normal range 0.90 to 1.26), and activated partial thromboplastin time (aPTT) of 28 seconds (normal range 25 to 45 seconds). Serological tests for B and C hepatitis, HIV, HTLV, CMV, and VDRL were all negative.
The patient underwent coronary angiography two hours after receiving 10 units of platelets. The right femoral artery (RFA) approach was used, according to Judkin's technique, using 6F introducer and catheters. The introducer was removed from the RFA immediately after the procedure, and local compression was applied during 20 minutes. Neither bleeding nor hematoma occurred after compression. The examination showed 80% stenosis in the right coronary artery (RCA) ostium, the reference diameter of which was 3.05 mm (
Six days after a daily regimen of clopidogrel 75 mg and two hours after another 10-unit platelet transfusion, a 3.0 x 10 mm LEKTON stent was successfully implanted in the RCA ostium, with its proximal end about 1 mm within the aorta (
Hospital course was uneventful. Seven days after stent implantation, the patient was discharged on clopidogrel 75 mg daily for another 17 days in order to ensure 30 days of continuous use. Within two weeks of clopidogrel therapy, platelet count remained stable at 40,000/mm³.
The patient became asymptomatic and, six months after stent implantation, underwent exercise stress testing, which showed ST-segment depression in the inferior leads. Another catheterization was performed two hours after platelet transfusion (eight units), using the right femoral artery (RFA) approach. A 70% in-stent restenosis was found (
The association of thrombocytopenia due to myelodysplastic syndrome and coronary disease is rare, and published data on the management of obstructive lesions through PCI in patients with low platelet count are scarce. The medical literature describes two patients with
In addition to the myelodysplastic syndrome, this patient had upper extremity phocomelia, a congenital disorder characterized by bilateral absence of the radius. An association of phocomelia with thrombocytopenia and a decrease in the number of megakaryocytes on the myelogram was described, the TAR syndrome (Thrombocytopenia with Absent Radius), a rare congenital disorder that differs from the myelodysplastic syndrome in that no changes occur in granulocytic and erythroid series5. Based on absolute platelet count, thrombocytopenia may be divided into the following categories: mild (<150,000/mm³), moderate (50–100,000 /mm³), severe (20–50,000/mm³) and profound (< 20,000/mm³). The non-linearity of the bleeding time associated with thrombocytopenia of different etiology and defined value was demonstrated by Harker. This accounts for the differences in absolute platelet count found in medical guides regarding indication for platelet transfusion in patients with thrombocytopenia of different etiologies6. According to America's Blood Centers, platelet transfusion should be administered prophylactically to patients with platelet count lower than 50,000/mm3 and who are undergoing surgery or an invasive procedure in which the operative field can be visualized or external pressure may be used to maintain hemostasis7.
In the present case, platelet count was 40,000/mm³, and the patient was given 10 units of platelets two hours before the procedures to increase platelet levels above 50,000/mm³. This measure has proved to be safe both for coronary angiography and stent implantation.
The use of heparin at 100 IU/kg during the procedure has also proved to be safe, since the introducer was removed from the femoral artery four hours postprocedure without bleeding or hematoma formation.
The use of small diameter introducers and catheters is recommended to facilitate postprocedural hemostasis. In the present case a 6F material was employed, because this is the smallest diameter available. The femoral artery was the chosen approach, since it is the technique used by our hemodynamic team. The radial artery is an alternative approach for patients with thrombocytopenia, but it is not routinely used at our institution8.
Clinical trials have shown higher restenosis rate in patients with aorto-ostial location after bare-metal stent implantation. In an observational study, drug-eluting stent implantation in patients with aorto-ostial lesions has yielded encouraging results, with 6.3% target-vessel revascularization. In this patient, drug-eluting stent was not used for economic reasons.
Atherosclerotic plaque fissuring or rupture is the most important pathophysiological mechanism of unstable angina. Platelet adhesion and aggregation and thrombus formation following plaque rupture, as well as hemorrhage and edema within the plaque, further aggravates stenosis10. In spite of the thrombocytopenia, this patient evolved with progressively unstable angina, suggesting that regardless of the small number of platelets, platelet function remained normal, thereby justifying the use of antiplatelet agents to prevent acute or subacute post-stent thrombosis. Among antiplatelet agents, clopidogrel alone was the treatment of choice, because this drug is better tolerated than ticlopidine. In addition, the combination of clopidogrel and aspirin is associated to higher risk of gastrointestinal bleeding in patients with thrombocytopenia and past history of gastritis, spontaneous gum bleeding, and petechiae11.
Thrombocytopenia, kept at around 20,000/ mm³, failed to protect against restenosis six months after stent implantation. In animal models, intimal hyperplasia inhibition was correlated to the degree of thrombocytopenia. Induced thrombocytopenia at less than 7,000/mm³ two or three days before balloon injury was necessary to inhibit neointimal formation in animals. Induced thrombocytopenia to prevent restenosis is clinically impracticable, and there are few data in the medical literature regarding clinical course after percutaneous coronary intervention in patients with low platelet count. Clinical trials have failed to demonstrate any beneficial effect of antiplatelet drugs in restenosis following angioplasty, although acute complications were reduced12.
This case report suggests that both angiography and percutaneous coronary intervention in patients with thrombocytopenia are safe procedures, provided that prophylactic platelet transfusion is performed two hours before; in the long term, however, restenosis may occur.
George César Ximenes Meireles Rua Sena Madureira, 1265/102 04021-051 – São Paulo, SP, Brazil E-mail:
Manuscript received December 7, 2004; revised Manuscript received June 24, 2004; accepted February 24, 2006.