Weight-Adjusted and Activated Clotting Time–Guided Heparinization Might Reduce the Postprocedural Hemorrhage in Percutaneous Transluminal Angioplasty for Acute Middle Cerebral Artery Occlusion
To the Editor:
We were impressed by the novel approach to treat acute ischemic stroke due to middle cerebral artery (MCA) occlusion proposed by Dr Nakano and coworkers.1 Instead of intravenous thrombolytic therapy, they had treated such disease with intra-arterial reperfusion therapy in 70 consecutive patients, 34 of whom with direct percutaneous transluminal angioplasty (PTA) over the infarct-related artery (IRA) and the remaining 36 with thrombolytic therapy alone. They found that the PTA group had not only higher IRA patency rate (91.2% versus 63.9%, P<0.01) but also better neurological result (modified Rankin Scale score 0-1 52.9% versus 41.7%) than the thrombolytic one. Besides, the incidence of large parenchyma hematoma was much lower in the PTA group (2.9% versus 19.4%, P=0.03). However, both their arms (PTA or thrombolytic) had a significantly high hyperdensity rate (47.1% and 63.9%, respectively), which represented prolonged (>24 hours) contrast medium extravasation or minor bleeding after the procedure. Consequently, the authors proposed that the direct PTA is an effective alternative to intra-arterial thrombolysis for MCA trunk occlusion.
To our surprise is the principle of anticoagulant dosage the authors used, which is quite different from that used in conventional percutaneous coronary intervention (PCI). Nakano et al tended to use a fixed heparin dose (5000 U before the procedure and 1000 U 1 hour later, both intravenously). As with the arrival of activated clotting time (ACT) in 1980s, the interventional cardiologists gradually abandoned the habit of giving standard heparin dose as in early years. From the work of Ferguson et al,2,3 it was found that patients having experienced periprocedural complications had a higher rate of ACT <250 s than the patients with a uneventful course (61% versus 27%, P<0.001). Furthermore, complications occurred in all patients with ACT <250 s, but in only 0.3% with a final ACT >300 s. It would be difficult to achieve desirable intravascular anticoagulation without complication using fixed-dosed heparinization without the ACT guide. Therefore, the routine heparinization of PCI recommended by the ACC/AHA guidelines4 should start with a weight-adjusted loading dose (50 to 70 U/kg) followed by complimentary ones guided by regular ACT assay every 5 to 10 minutes to keep it above 250 s. According to this rule, and assuming the patient weighs an average of 50 to 70 kg (not described in the article), the heparinization had been most likely over the desired range.
Despite the promising neurological result after reperfusion therapy, both their arms (PTA or thrombolytic) have a significantly high hyperdensity rate ( 47.1% and 63.9%, respectively), which represented prolonged (>24 hours) contrast medium extravasation after the procedure by the authors’ definition. Furthermore, more than one third of patients had definite hemorrhage (10/34 and 13/36, respectively). As a result, we wonder whether a much lower bleeding rate could be attained, had the dose of anticoagulant been adjusted with the body weight and guided by ACT.
Encouraged by the authors’ exciting experience, we performed an emergent PTA in a 32-year-old woman with rheumatic heart disease and atrial fibrillation. Sudden onset of complete consciousness loss, right hemiplegia, and conjugated leftward eye gazing (NIHSS 30) occurred, and brain CT showed no evidence of bleeding. Cerebral angiography (4 hours after onset) showed a total occlusion over the left MCA proximal to the lenticulostriate arteries, so PTA was performed then. Considering the dosage principle of heparin discussed above, we gave a 70-U/kg loading dose and maintained ACT >250 s with a HemoTec device throughout the procedure (277 s at the end of the procedure). Then, after the guiding wire (0.014 inch) passed the lesion with ballooning (2.5 mm×20 mm up to 10 ATM) twice, we restored TIMI III flow over the whole territory of MCA 4.5 hours after stroke onset. Immediately after the procedure, the patient regained neutral position of her eyeballs and began to respond to verbal stimuli. Soon thereafter, muscle power and consciousness improved as well, and the NIHSS 24 hours after PTA was only 4. To our satisfaction, the follow-up CT showed only hypodensity without evidence of bleeding.
Although more experience is necessary to decide the adequate dosing formula of heparin, the conventional rule being used in PCI and recommended in ACC/AHA guidelines might be applied in PTA for acute MCA occlusion with fewer postprocedural complications.
Nakano S, Iseda T, Yoneyama T, Kawano H, Wakisaka S. Direct percutaneous transluminal angioplasty for acute middle cerebral artery trunk occlusion: an alternative option to intra-arterial thrombolysis. Stroke. 2002; 33: 2872–2876.
Smith SC Jr, Dove JT, Jacobs AK, Kennedy JW, Kereiakes D, Kern MJ, Kuntz RE, Popma JJ, Schaff HV, Williams DO. ACC/AHA guidelines for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1993 Guidelines for Percutaneous Transluminal Coronary Angioplasty). J Am Coll Cardiol. 2001; 37: 2239i–lxvi.
We appreciate the interesting response of Dr Li and coauthors, describing the importance of weight-adjusted and activated clotting time (ACT)–guided heparinization during direct percutaneous transluminal angioplasty (PTA) for acute middle cerebral artery occlusion to reduce postprocedural hemorrhagic complications. They raise a high rate of postprocedural hyperdensity on CT in our study, which may result from the use of a fixed heparin dose. We agree that ACT-guided heparinization is better. However, I do not think that our method of heparin use may increase the rate of hemorrhagic complications. Since we performed CT just after recanalization therapy in all cases, the rate of hyperdensity was as high as 47.1% (16/34) even in the PTA group. But 50% of those hyperdensities disappeared within 24 hours, suggesting contrast stagnation or extravasation instead of hemorrhage. Among the 10 patients with actual hemorrhagic transformations, 6 had only petechial hemorrhage and 2 of them appeared later in spite of no contrast extravasation just after direct PTA. These petechial hemorrhages are often seen in the subacute stage of stroke even without heparin use. The rate of parenchymal hematoma was 11.8% (4/34) and that of symptomatic hemorrhage with neurological worsening was only 2.9% (1/34). We think that these rates of hemorrhagic transformations are reasonable and acceptable. Anyway, further efforts to reduce hemorrhagic complications should be needed and we are going to try ACT-guided heparin use according to the kind recommendation by Li et al.
They describe a case of successful recanalization by direct PTA with an excellent clinical result. It is our privilege to know that our recanalization method is being used as a helpful treatment.
Thank you, Dr Li and coworkers, for your letter.