Catheterization and Cardiovascular Diagnosis 23:141-143 (1991)
In Vivo Thrombus Formation on a Guidewire During lntravascular Ultrasound Imaging: Evidence for Inadequate Heparinization Paul A. Grayburn, MD, John E. Willard, MD, M. Elizabeth Brickner, MD, and Eric J. Eichhorn, MD We present a case in which thrombus formation on a guidewire was visualized during intravascular ultrasound imaging despite the administration of 10,000 units of heparln sulfate prior to the procedure. Gross thrombus formation was confirmed upon removal of the guidewire. The activated clotting time was found to be 191 8, suggesting heparin resistance. Thls report graphically illustrates the potential thrombogenicity associated with intravascular guidewire manipulation during procedures such as intravascular ultrasound imaging and percutaneous transluminal coronary angioplasty. Moreover, this case suggests that adequate heparinization should be routinely verified by measuring the activated clotting time prior to introducing a guidewire into the arterial system. Key words: echocardiography, coronary artery disease, anticoagulation
INTRODUCTION
with non-specific ST-T wave changes. The patient was treated with aspirin, nitrates, and diltiazem prior to cathThe recent development of intravascular ultrasound eterization. He did not receive intravenous heparin. Inimaging has provided an exciting new tool for the evalformed consent was obtained both for heart catheterizauation of cardiovascular pathology. In vitro studies have tion and for intravascular ultrasound imaging according demonstrated the ability of this technique to distinguish to a protocol approved by our institutional review board. the three layers (intima, media, and adventitia) of musUsing the Seldinger technique, 8F sheaths were placed in cular arteries [ 11, as well as to differentiate between calthe right femoral vein and artery. A 10,000 unit bolus of cified, lipid-laden, and fibrous plaque in coronary artery heparin sulfate was given through the venous sheath. A specimens [2]. Accordingly, intravascular ultrasound of6F intravascular ultrasound catheter (Boston Scientific) fers great promise as a means of evaluating lesion morinterfaced to an imaging console (IVUS, Diasonics, Inc.) phology and assessing the efficacy of therapeutic interwas advanced through the arterial sheath for imaging of ventions in patients with coronary artery disease or the thoracic and abdominal aorta prior to coronary artery peripheral vascular disease. In vivo applications of inangiography. This system uses a 20 MHz mechanical travascular ultrasound to the imaging of coronary arteries transducer rotating at 900 rpm to provide cross-sectional involve passage of the imaging catheter over a guidewire images at a 10 degree look-forward angle. The imaging using techniques commonly employed during percutanecatheter is advanced over a guidewire using a ous transluminal coronary angioplasty (PTCA). Because “monorail” design similar to that used for coronary anof the potential thrombogenicity of an intravascular gioplasty catheters. In this patient, a standard 0.016 in guidewire, we routinely administer a bolus of 10,000 non-coated guidewire (Advanced Catheter Systems) was units of heparin sulfate intravenously prior to both PTCA used. High quality images of the aorta were easily oband intravascular ultrasound imaging. This report describes visualization of thrombus formation on the guidewire during intravascular ultrasound imaging. CASEREPORT
A 43-yr-old man underwent diagnostic left heart catheterization for evaluation of unstable angina. Physical examination, chest x-ray, and laboratory studies were all normal. The electrocardiogram revealed sinus rhythm 0 1991 Wiley-Liss, Inc.
From the Department of Internal Medicine (Cardiology Division), Veteran’s Affairs Medical Center and University of Texas Southwestern Medical School, Dallas, Texas.
Received October 29, 1990; revision accepted December 6, 1990. Address reprint requests to Paul A. Grayburn, M.D., Division of Cardiology (111A), VA Medical Center, 4500 S . Lancaster Road, Dallas TX 75216.
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Fig. 1. Left: lntravascular ultrasound image from the aorta prior to thrombus formation. The ultrasound catheter appears as the circular black structure within the vessel lumen. The catheter is surrounded by a bright “ring-down” artifact. The arrow
points to the guidewire echo, which is small and normal in appearance. Right: lntravascular ultrasound image taken minutes later showing a large hazy echo density representing thrombus (arrow) attached to the guidewire.
tained and within 5 min an unexpected echo reflectance with acoustic properties suggestive of thrombus was seen in the region of the guidewire (Fig. 1). The imaging catheter and guidewire were removed and examination of the guidewire revealed gross thrombus (Fig. 2). The activated clotting time was assessed by an automated coagulation timing instrument (Hemochron) and was 191 s, considerably shorter than the 3 0 0 s recommended for adequate heparinization [ 3 ] . After administration of additional heparin, the catheterization was completed as planned. There was no clinical evidence of any thromboembolic complications. DISCUSSION
The importance of heparin in preventing thrombus formation and/or acute closure during PTCA is well recognized [4-61. Accordingly, most laboratories administer a bolus of 10,OOO units of heparin prior to placement of a guidewire in the coronary artery during PTCA. However, an adequate anticoagulant effect will not be achieved in all patients unless higher doses are used. Ogilby et al. showed that 11% of subjects undergoing PTCA had an activated clotting time less than 300 s following a 10,000unit bolus of heparin sulfate [ 3 ] . Bull et al. reported a wide range of heparin requirements for patients undergoing extracorporeal circulatory support during bypass surgery [7]. Reasons for heparin resistance include antithrombin I11 deficiency, heparin antibodies, oral contraceptives, endocarditis, pregnancy, shock, hypereosinophilic syndrome, disseminated intravascular
Fig. 2. Photograph of the guidewire after removal from the body. Gross thrombus formation was evident (arrow).
coagulation, increased factor VIII levels, accelerated heparin clearance, and intraaortic balloon counterpulsation [8]. Regardless of cause, inadequate heparinization during intravascular procedures such as PTCA or intravascular ultrasound imaging has potentially disastrous consequences, including embolization and acute closure of the coronary artery with subsequent myocardial infarction and even death.
Thrombus Formation During IVUS
This case report graphically documents in vivo clot formation on a guidewire during intravascular ultrasound imaging. Sheikh et al. [9] reported a similar case in which thrombus was seen at the catheter tip during intravascular ultrasound imaging despite prior heparinization. Such findings emphasize the need for assessment of heparin effect prior to intravascular guidewire placement. We now measure the activated clotting time 5 min after the initial heparin bolus during PTCA or intravascular ultrasound imaging. If the activated clotting time is at least 300 s, intravascular guidewire manipulation can be safely initiated. If the activated clotting time is less than 300 s, additional heparin boluses units are necessary to achieve adequate heparinization [3]. Certain design features of the ultrasound imaging catheter and/or guidewire could have contributed to the formation of the thrombus. The monorail sleeve of the imaging catheter is shorter than that of comparable PTCA catheters, such that a greater length of guidewire is exposed to the circulation. It is possible that over-the-wire catheters, in which less guidewire is exposed, are less prone to thrombus development. Moreover, we used a non-coated guidewire, which may be more thrombogenic than coated guidewires. Finally, it is conceivable that mechanical rotation of the core element could have potentiated thrombus formation by heat generation. Despite these considerations, we believe that heparin resistance is the predominant mechanism underlying the formation of thrombus on the guidewire in this case. This case lends strong support to the practice of routinely assessing the adequacy of heparinization prior to intravascular guidewire placement.
143
REFERENCES 1. Gussenhoven EJ, Essed CE, Lancee CT, Mastik F, Frietman P,
Van Egmond FC, Reiber J , Bosch H, Van Urk H, Roelandt J, Bom N: Arterial wall characteristics determined by intravascular ultrasound imaging: an in vitro study. J Am Coll Cardiol 14:947-52, 1989. 2. Potkin BN, Bartorelli AL, Gessert JM, Neville RF, Almagor Y , Roberts WC, Leon MC: Coronary artery imaging with intravascular high-frequency ultrasound. Circulation 8 1: I575-85, 1990. 3. Ogilby JD, Kopelman HA, Klein LW, Agarwal JB: Adequate heparinization during PTCA: assessment using activated clotting times. Cath Cardiovasc Diag 18:206-9, 1989. 4. Heras M, Chesebro JH, Penny WJ, Bailey KR, Lam JYT, Holmes DR, Reeder GS, Badimon L, Fuster V: Importance of adequate heparin dosage in arterial angioplasty in a porcine model. Circulation 78:654-60, 1988. 5 . Ellis SG, Roubin GS, King SB, Douglas JS, Weintraub WS, Thomas RG, Cox WR: Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. Circulation 77:312-19, 1988. 6. Gabliani G , Deligonal U, Kern MJ, Vandormael M: Acute coronary occlusion after successful percutaneous transluminal coronary angioplasty : temporal relationship to discontinuation of anticoagulation. Am Heart J 116:696-700, 1988. I. Bull BS, Korman RA, Huse WM, Briggs BD: Heparin therapy during extracorporeal circulation. 1 . Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg 69:674-84, 1975. 8. Miller RD: Heparin resistance prior to cardiopulmonary bypass. Anesthesiology 64504-7, 1986. 9. Sheikh KH, Kisslo K, Davidson CJ: Interventional applications of intravascular ultrasound imaging: initial experience and future perspectives. Echocardiography 7:433-41, 1990.
In Vivo Thrombus Formation on a Guidewire During lntravascular Ultrasound Imaging: Evidence for Inadequate Heparinization Paul A. Grayburn, MD, John E. Willard, MD, M. Elizabeth Brickner, MD, and Eric J. Eichhorn, MD We present a case in which thrombus formation on a guidewire was visualized during intravascular ultrasound imaging despite the administration of 10,000 units of heparln sulfate prior to the procedure. Gross thrombus formation was confirmed upon removal of the guidewire. The activated clotting time was found to be 191 8, suggesting heparin resistance. Thls report graphically illustrates the potential thrombogenicity associated with intravascular guidewire manipulation during procedures such as intravascular ultrasound imaging and percutaneous transluminal coronary angioplasty. Moreover, this case suggests that adequate heparinization should be routinely verified by measuring the activated clotting time prior to introducing a guidewire into the arterial system. Key words: echocardiography, coronary artery disease, anticoagulation
INTRODUCTION
with non-specific ST-T wave changes. The patient was treated with aspirin, nitrates, and diltiazem prior to cathThe recent development of intravascular ultrasound eterization. He did not receive intravenous heparin. Inimaging has provided an exciting new tool for the evalformed consent was obtained both for heart catheterizauation of cardiovascular pathology. In vitro studies have tion and for intravascular ultrasound imaging according demonstrated the ability of this technique to distinguish to a protocol approved by our institutional review board. the three layers (intima, media, and adventitia) of musUsing the Seldinger technique, 8F sheaths were placed in cular arteries [ 11, as well as to differentiate between calthe right femoral vein and artery. A 10,000 unit bolus of cified, lipid-laden, and fibrous plaque in coronary artery heparin sulfate was given through the venous sheath. A specimens [2]. Accordingly, intravascular ultrasound of6F intravascular ultrasound catheter (Boston Scientific) fers great promise as a means of evaluating lesion morinterfaced to an imaging console (IVUS, Diasonics, Inc.) phology and assessing the efficacy of therapeutic interwas advanced through the arterial sheath for imaging of ventions in patients with coronary artery disease or the thoracic and abdominal aorta prior to coronary artery peripheral vascular disease. In vivo applications of inangiography. This system uses a 20 MHz mechanical travascular ultrasound to the imaging of coronary arteries transducer rotating at 900 rpm to provide cross-sectional involve passage of the imaging catheter over a guidewire images at a 10 degree look-forward angle. The imaging using techniques commonly employed during percutanecatheter is advanced over a guidewire using a ous transluminal coronary angioplasty (PTCA). Because “monorail” design similar to that used for coronary anof the potential thrombogenicity of an intravascular gioplasty catheters. In this patient, a standard 0.016 in guidewire, we routinely administer a bolus of 10,000 non-coated guidewire (Advanced Catheter Systems) was units of heparin sulfate intravenously prior to both PTCA used. High quality images of the aorta were easily oband intravascular ultrasound imaging. This report describes visualization of thrombus formation on the guidewire during intravascular ultrasound imaging. CASEREPORT
A 43-yr-old man underwent diagnostic left heart catheterization for evaluation of unstable angina. Physical examination, chest x-ray, and laboratory studies were all normal. The electrocardiogram revealed sinus rhythm 0 1991 Wiley-Liss, Inc.
From the Department of Internal Medicine (Cardiology Division), Veteran’s Affairs Medical Center and University of Texas Southwestern Medical School, Dallas, Texas.
Received October 29, 1990; revision accepted December 6, 1990. Address reprint requests to Paul A. Grayburn, M.D., Division of Cardiology (111A), VA Medical Center, 4500 S . Lancaster Road, Dallas TX 75216.
142
Grayburn et al.
Fig. 1. Left: lntravascular ultrasound image from the aorta prior to thrombus formation. The ultrasound catheter appears as the circular black structure within the vessel lumen. The catheter is surrounded by a bright “ring-down” artifact. The arrow
points to the guidewire echo, which is small and normal in appearance. Right: lntravascular ultrasound image taken minutes later showing a large hazy echo density representing thrombus (arrow) attached to the guidewire.
tained and within 5 min an unexpected echo reflectance with acoustic properties suggestive of thrombus was seen in the region of the guidewire (Fig. 1). The imaging catheter and guidewire were removed and examination of the guidewire revealed gross thrombus (Fig. 2). The activated clotting time was assessed by an automated coagulation timing instrument (Hemochron) and was 191 s, considerably shorter than the 3 0 0 s recommended for adequate heparinization [ 3 ] . After administration of additional heparin, the catheterization was completed as planned. There was no clinical evidence of any thromboembolic complications. DISCUSSION
The importance of heparin in preventing thrombus formation and/or acute closure during PTCA is well recognized [4-61. Accordingly, most laboratories administer a bolus of 10,OOO units of heparin prior to placement of a guidewire in the coronary artery during PTCA. However, an adequate anticoagulant effect will not be achieved in all patients unless higher doses are used. Ogilby et al. showed that 11% of subjects undergoing PTCA had an activated clotting time less than 300 s following a 10,000unit bolus of heparin sulfate [ 3 ] . Bull et al. reported a wide range of heparin requirements for patients undergoing extracorporeal circulatory support during bypass surgery [7]. Reasons for heparin resistance include antithrombin I11 deficiency, heparin antibodies, oral contraceptives, endocarditis, pregnancy, shock, hypereosinophilic syndrome, disseminated intravascular
Fig. 2. Photograph of the guidewire after removal from the body. Gross thrombus formation was evident (arrow).
coagulation, increased factor VIII levels, accelerated heparin clearance, and intraaortic balloon counterpulsation [8]. Regardless of cause, inadequate heparinization during intravascular procedures such as PTCA or intravascular ultrasound imaging has potentially disastrous consequences, including embolization and acute closure of the coronary artery with subsequent myocardial infarction and even death.
Thrombus Formation During IVUS
This case report graphically documents in vivo clot formation on a guidewire during intravascular ultrasound imaging. Sheikh et al. [9] reported a similar case in which thrombus was seen at the catheter tip during intravascular ultrasound imaging despite prior heparinization. Such findings emphasize the need for assessment of heparin effect prior to intravascular guidewire placement. We now measure the activated clotting time 5 min after the initial heparin bolus during PTCA or intravascular ultrasound imaging. If the activated clotting time is at least 300 s, intravascular guidewire manipulation can be safely initiated. If the activated clotting time is less than 300 s, additional heparin boluses units are necessary to achieve adequate heparinization [3]. Certain design features of the ultrasound imaging catheter and/or guidewire could have contributed to the formation of the thrombus. The monorail sleeve of the imaging catheter is shorter than that of comparable PTCA catheters, such that a greater length of guidewire is exposed to the circulation. It is possible that over-the-wire catheters, in which less guidewire is exposed, are less prone to thrombus development. Moreover, we used a non-coated guidewire, which may be more thrombogenic than coated guidewires. Finally, it is conceivable that mechanical rotation of the core element could have potentiated thrombus formation by heat generation. Despite these considerations, we believe that heparin resistance is the predominant mechanism underlying the formation of thrombus on the guidewire in this case. This case lends strong support to the practice of routinely assessing the adequacy of heparinization prior to intravascular guidewire placement.
143
REFERENCES 1. Gussenhoven EJ, Essed CE, Lancee CT, Mastik F, Frietman P,
Van Egmond FC, Reiber J , Bosch H, Van Urk H, Roelandt J, Bom N: Arterial wall characteristics determined by intravascular ultrasound imaging: an in vitro study. J Am Coll Cardiol 14:947-52, 1989. 2. Potkin BN, Bartorelli AL, Gessert JM, Neville RF, Almagor Y , Roberts WC, Leon MC: Coronary artery imaging with intravascular high-frequency ultrasound. Circulation 8 1: I575-85, 1990. 3. Ogilby JD, Kopelman HA, Klein LW, Agarwal JB: Adequate heparinization during PTCA: assessment using activated clotting times. Cath Cardiovasc Diag 18:206-9, 1989. 4. Heras M, Chesebro JH, Penny WJ, Bailey KR, Lam JYT, Holmes DR, Reeder GS, Badimon L, Fuster V: Importance of adequate heparin dosage in arterial angioplasty in a porcine model. Circulation 78:654-60, 1988. 5 . Ellis SG, Roubin GS, King SB, Douglas JS, Weintraub WS, Thomas RG, Cox WR: Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. Circulation 77:312-19, 1988. 6. Gabliani G , Deligonal U, Kern MJ, Vandormael M: Acute coronary occlusion after successful percutaneous transluminal coronary angioplasty : temporal relationship to discontinuation of anticoagulation. Am Heart J 116:696-700, 1988. I. Bull BS, Korman RA, Huse WM, Briggs BD: Heparin therapy during extracorporeal circulation. 1 . Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg 69:674-84, 1975. 8. Miller RD: Heparin resistance prior to cardiopulmonary bypass. Anesthesiology 64504-7, 1986. 9. Sheikh KH, Kisslo K, Davidson CJ: Interventional applications of intravascular ultrasound imaging: initial experience and future perspectives. Echocardiography 7:433-41, 1990.
