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Severe thrombocytopenia (TP) is a relatively rare finding, particularly in patients with coronary artery disease. Percutaneous coronary intervention (PCI) has traditionally not been an option for patients with severe TP, because these patients are felt to be at increased risk for bleeding complications resulting from the required periprocedural anticoagulation and postprocedural dual antiplatelet therapy (DAPT). This speculation is indirectly supported by a recent study in which the baseline TP emerged as an independent predictor of mortality in patients undergoing PCI [1]. Therefore, we collected data from 35 patients with severe TP undergoing PCI, illustrating their medical and interventional management as well as their clinical outcome.

From January 2006 to December 2010, 5170 patients received PCI in our institute. Thirty-five (0.6%) of these patients had a previous diagnosis of severe TP. Fifteen (43%) had immune thrombocytopenic purpura, five (14%) had chronic lymphocytic leukemia, three (8%) had chronic myeloid leukemia, two (6%) had chronic kidney disease (one during immunosuppressive therapy after transplantation), and 10 (28%) had chronic liver disease. Severe TP is defined as a persistent platelet count of < 50 × 109 L−1. Our institute has an guideline for the management of patients with severe TC that is briefly described below. The recommended medical and interventional strategy was bare metal stent (BMS) implantation, followed by DAPT for 1 month. After DAPT discontinuation, at least one antiplatelet drug (aspirin 75 mg) was recommended for life. Periprocedural antithrombotic drugs were administered according to the operator’s choice. Glycoprotein (GP)IIb–IIIa inhibitor use was discouraged. Nevertheless, each operator was free to choose, for each specific patient, the stent type and antiplatelet/antithrombotic therapy during and after PCI. The radial artery was selected as the first-choice access site. In all patients, platelet function was assessed before PCI with aspirin and P2Y12 VerifyNow (Accumetrics, San Diego, CA, USA) [2]. The results were expressed in aspirin reaction units (ARU) and P2Y12 reaction units (PRU), respectively [2]. Patients with ARU > 550 and PRU > 230 were considered to be aspirin and clopidogrel poor responders, respectively. Patients underwent outpatient visits every 6 months. The ischemic clinical endpoints were death, myocardial infarction (MI), stent thrombosis, and target vessel revascularization. Bleeding complications were classified according to the Thrombolysis In Myocardial Infarction classification and BleedScore [3]. This study was approved by the local Ethics Committee, and all patients gave written informed consent. Continuous data were presented as means ± standard deviations, and were compared by use of the t-test. Categorical variables were summarized in terms of numbers and percentages, and were then compared by use of the two-sided Fisher exact test. A P-value of < 0.05 was considered to be significant. Analysis was performed with statistica 8 (StatSoft Inc., Tulsa, OK, USA).

Table 1 shows all available data for the study population. As expected, the cardiovascular risk factors were frequent. Nevertheless, the number of prior cardiovascular events was relatively low. The radial artery was used as the access site in all patients, with the exception of one. This patient’s coronary artery angiography was performed by radial access, but the 7F guiding catheter was necessary for the performance of left main stenting, and so the femoral artery was used. Drug-eluting stents were used in only five patients, principally in the left main artery or in long lesions of the left anterior descending artery. The antithrombotic agent most commonly used was unfractioned heparin. Only in the last year was bivalirudin chosen for three patients. A GPIIb–IIIa inhibitor (bciximab) was used only in one patient presenting with ST-segment elevation MI. In this case, the operator was unaware of the existence of severe TP. Administration of immune globulin to increase the platelet count before PCI was used in five patients (platelet count from 24 ± 3 to 37 ± 6 U × 10L−1). We suggested monotherapy with clopidogrel in seven (20%) patients. In one of these patients, clopidogrel was stopped after 7 months because of bleeding complications (no ischemic events were reported after clopidogrel discontinuation). In seven (20%) patients, we recommended 6 months of DAPT, but only five completed the planned course. Overall, 25 patients of 28 (89%; 95% confidence interval [CI] 72–97%) completed the planned course of DAPT. At 1 year, one antiplatelet drug was maintained in 27 (77%; 95% CI 59–89%) patients. As expected, the number of poor responders was very low. We did not find aspirin poor responders, and only one patient was a clopidogrel poor responder. Overall, we reported four (11%) ischemic adverse events. One death occurred suddenly at 13 months after PCI, and the other occurred at 8 months after PCI as a consequence of end-stage chronic leukemia. One MI was attributable to stent thrombosis (BMS, 3 months after PCI) in a patient taking aspirin, and the other was a spontaneous MI 6 months after PCI in a different coronary artery. Almost half of our study population experienced a bleeding complication. The majority of these adverse events were superficial bleeds (petechiae and ecchymosis). Regarding the most serious events, three occurred during DAPT, one during clopidogrel intake, and two during aspirin intake. We principally observed gastrointestinal and genitourinary bleeds. At the time of bleeding, antiplatelet drugs were discontinued. No intracranial hemorrhage was reported. In two cases, the blood loss was very significant (> 6 g dL−1 hemoglobin), requiring red blood cell transfusions.

Table 1.   Characteristics of the patients
CharacteristicsAll (n = 35)Patients with ITP (n = 15)Patients with platelets < 30 000 (n = 9)Patients with platelets 30 000–50 000 (n = 26)P*
  1. ARU, aspirin reaction unit; CABG, coronary artery bypass graft; DAPT, dual antiplatelet therapy; GP, glycoprotein; ITP, immune thrombocytopenic purpura; MI, myocardial infarction; NSTEACS, non-ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; PRU, P2Y12 reaction unit; SD, standard deviation; STEMI, ST-segment elevation myocardial infarction; TIA, transient ischemic attack; TIMI, Thrombolysis In Myocardial Infarction; TVR, target vessel revascularization; UFH, unfractioned heparin. *P-value for the comparison of patients with platelets < 30 000 vs. those with 30–50 000. Alarming: transfusion needed, intracranial, life-threatening. Internal: hematoma, epistaxis, blood loss from mouth, vagina, melena, eye bleed, hematuria, hematemesis. Superficial: easy bruising, bleeding from small cuts, petechiae, ecchymosis.

Age (years), mean ± SD70 ± 1369 ± 1267 ± 1372 ± 130.3
Men, no. (%)28 (80)12 (80)6 (67)22 (85)0.4
Diabetes mellitus, no. (%)8 (23)2 (13)3 (33)5 (19)0.4
Hypertension, no. (%)28 (80)10 (67)7 (78)21 (81)0.6
Current smoker, no. (%)5 (14)1 (67)1 (11)4 (15)0.8
Hypercholesterolemia, no. (%)16 (46)5 (33)5 (55)11 (42)0.7
Medical history
 CABG, no. (%)0 (0)0 (0)0 (0)0 (0)0.9
 PCI, no. (%)2 (6)0 (0)0 (0)2 (8)0.6
 MI, no. (%)1 (3)0 (0)0 (0)1 (4)0.5
 TIA/stroke, no. (%)0 (0)0 (0)0 (0)0 (0)0.9
 Time from diagnosis of ITP (years), mean ± SD28 ± 12
 Splenectomy, no. (%)13 (87)
 Corticosteroid therapy, no. (%)11 (73)
 Immunosuppressive therapy, no. (%)4 (27)
Clinical presentation
 Silent ischemia/stable angina, no. (%)13 (37)9 (60)3 (33)10 (38)0.5
 NSTEACS, no. (%)17 (48)5 (33)5 (55)12 (46)0.2
 STEMI, no. (%)5 (14)1 (7)1 (11)4 (15)0.5
Angiographic and procedural data
 Radial access, no. (%)34 (97)15 (100)9 (100)25 (96)0.8
 Multivessel disease, no. (%)14 (40)6 (40)4 (44)10 (38)0.7
 Target vessel of PCI
  Left main artery, no. (%)3 (9)1 (7)0 (0)3 (11)0.8
  Left anterior descending artery, no. (%)19 (54)9 (60)6 (67)13 (50)0.6
  Right coronary artery, no. (%)10 (28)4 (27)2 (22)8 (31)0.7
  Circumflex artery, no. (%)10 (28)4 (27)4 (44)6 (23)0.5
 Nominal stent diameter (mm), mean ± SD2.9 ± 0.53 ± 0.73 ± 0.52.9 ± 0.60.9
 Total stent length (mm), mean ± SD24 ± 1023 ± 1325 ± 1124 ± 90.9
 Drug-eluting stent, no. (%)5 (14)2 (13)1 (11)4 (15)0.6
Laboratory data
 Platelets (U × 10L−1), mean ± SD38 ± 733 ± 828 ± 542 ± 8< 0.01
 Aspirin VerifyNow > 550 ARU, no. (%)0 (0)0 (0)0 (0)0 (0)0.9
 P2Y12 VerifyNow > 230 PRU, no. (%)1 (3)0 (0)(0)1 (4)0.8
Medical therapy
 During PCI
  UFH, no. (%)32 (91)13 (87)6 (67)26 (100)0.5
  Bivalirudin, no.(%)3 (9)2 (13)3 (33)0 (0)0.3
  GPIIb–IIIa inhibitors, no. (%)1 (3)0 (0)0 (0)1 (4)0.9
  Intravenous immune globulin, no. (%)5 (14)5 (33)5 (55)0 (0)< 0.01
 Antiplatelet therapy indication
  Monotherapy with clopidogrel, no. (%)7 (20)3 (20)5 (55)2 (8)0.03
  DAPT for 1 month, no. (%)21 (60)9 (60)3 (33)18 (69)0.05
  DAPT for 6 months, no. (%)7 (20)3 (20)1 (11)6 (23)0.3
 Chronic use of antiplatelet therapy
  DAPT for at least 1 month, no. (%)22 (63)10 (67)4 (44)18 (69)0.2
  DAPT for at least 6 months, no. (%)5 (14)2 (13)0 (0)5 (18)0.1
  One antiplatelet drug at 1 year, no. (%)28 (80)12 (80)7 (78)23 (88)0.6
Adverse events
 Follow-up (months), mean ± SD28 ± 928 ± 1029 ± 1028 ± 80.8
 Death, no. (%)2 (6)0 (0)1 (11)1 (4)0.6
 MI, no (%).2 (6)1 (6)0 (0)2 (8)0.9
 Death + MI, no. (%)4 (11)1 (6)1 (11)3 (11)0.2
 Definite stent thrombosis, no. (%)1 (3)0 (0)0 (0)1 (4)0.7
 TVR, no. (%)4 (11)1 (6)1 (11)3 (11)0.9
 Bleeds according to BleedScore, no. (%)17 (48)6 (40)7 (77)10 (38)0.3
  Alarming, no. (%)2 (6)1 (6)1 (11)1 (4)0.8
  Internal, no. (%)4 (11)1 (6)2 (22)2 (8)0.4
  Superficial, no. (%)11 (31)4 (27)4 (44)7 (27)0.3
 TIMI major, no. (%)2 (6)1 (6)1 (11)1 (4)0.8
 TIMI minor, no. (%)3 (8)1 (6)2 (22)1 (4)0.2

The TP that develops as a result of cardiac medications (principallyGPIIb–IIIa inhibitors) has been shown to be associated with more adverse events [4]. TP at admission to the intensive care unit emerged as a powerful predictor of higher in-hospital mortality [5]. Recently, TP at baseline (platelet count of < 150 × 10L−1) has been independently associated with an increased incidence of mortality in patients undergoing PCI [1]. An inverse relationship was found between in-hospital death, major adverse cardiac events and major bleeding rates on comparison with the platelet count [1]. Nevertheless, information on the medical and interventional treatments, the compliance with antiplatelet therapy and the occurrence of ischemic and bleeding complications in patients with TP and undergoing PCI is lacking. This is particularly the case if we consider patients with severe TP and longer follow-up. To the best of our knowledge, this is the first study to have prospectively collected, over a 5-year period, the baseline data and the long-term clinical follow-up of 35 patients with severe TP undergoing PCI. Overall, PCI in this particular subset of patients appears to be feasible and safe. The rate of periprocedural adverse events is very limited. In particular, the selection of the radial artery as the first-choice access site may be crucial to minimize complications. Also, ischemic adverse events are generally infrequent. Despite a considerable number of risk factors, previous cardiovascular events (MI and stroke) are rare, and recurrences after PCI are also infrequent. Although we principally used BMS, in-stent restenosis was not frequent. According to our protocol, these patients receive drug elutin stent (DES) only in very selected cases (left main artery, overlapping in left anterior descending artery, small vessels), and the low rate of in-stent restenosis indirectly supported this strategy. As expected, the main problem with this group of patients comprises the bleeding complications. Despite the conservative antiplatelet regimen (the majority of patients received DAPT for only 1 month, and 20% received monotherapy), we observed a very high rate of bleeding complications. This study population was closely monitored through frequent telephone contacts and clinical visits. This finding may explain the overall good compliance with antiplatelet therapy despite the high number of bleeding events. Previous studies reported a higher mortality rate in patients with TP [1–5]. Although our study is strongly limited by the small sample size, we suggest that careful treatment, monitoring and follow-up may reduce the occurrence of PCI-related bleeding and may improve compliance with antiplatelet therapy as well as minimizing the negative prognostic impact of bleeding events.

In conclusion, we found that, in patients with severe TP, PCI is feasible and generally well tolerated. The main drawbacks are the bleeding complications, which are frequent and may have a negative clinical impact. Careful management with the radial artery as the access site, BMS implantation and a short DAPT protocol may help to improve their outcome. Also, close monitoring is crucial to improve compliance with therapy and minimize adverse events.

Disclosure of conflict of interests

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  2. Disclosure of conflict of interests
  3. References

The authors state that they have no conflict of interest.

References

  1. Top of page
  2. Disclosure of conflict of interests
  3. References
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