Anesth Analg 2007;104:538-540
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000255155.87860.94
PEDIATRIC ANESTHESIA
The Hemostatic History of a 15-Month-Old Child Implanted with a Berlin Heart Left Ventricular Assist Device
Brad L. Steenwyk, MD*,
James K. Kirklin, MD
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William Q. Gurley, MD*, and
Vance G. Nielsen, MD*
From the Departments of *Anesthesiology and Surgery, The University of Alabama at Birmingham, Birmingham, Alabama.
Address correspondence and reprint requests to Vance G. Nielsen, MD, Department of Anesthesiology, The University of Alabama at Birmingham, Basic Medical Research Building II, Room 210, 901 19th St. South, Birmingham, AL 35294-2172. Address e-mail to vnielsen{at}uab.edu.
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Abstract
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We documented the hemostatic changes associated with placement of a EXCOR® Berlin Heart left ventricular assist device in a 15-month-old child before heart transplantation. The development of hypercoagulability was rapid, manifested first by a plasmatic and subsequently platelet-mediated increase in coagulation kinetics and strength that persisted for weeks. The patient had no thrombotic complications for 6 wk before transplant but required extraordinary blood product administration to achieve hemostasis secondary to aggressive, multimodal anticoagulation. In summary, when proscribing anesthetic and surgical management of patients with a Berlin Heart, consideration of hypercoagulable features and anticoagulant therapy must be made to maximize patient safety.
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Introduction
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Mechanical circulatory support for infants and small children has significantly evolved for over a decade, providing a bridge to transplantation or a period of support for myocardial recovery (1–5). However, device thrombosis and systemic thromboembolism have remained significant causes of morbidity and mortality despite aggressive anticoagulation (1–5), with complication rates (including neurologic events) between 50%–100%, similar to that observed in adults with device placement (6). To provide greater insight into this issue, we report the hemostatic changes associated with implantation and maintenance of a child with an EXCOR® Berlin Heart left ventricular assist device (LVAD; Berlin Heart, Berlin, Germany) for 6 wk before transplantation.
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CASE REPORT
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A 15-month-old child was admitted with congestive heart failure and a diagnosis of postviral dilated cardiomyopathy that rapidly progressed to cardiogenic shock. Extracorporeal membrane oxygenation was instituted and search initiated to identify a compatible donor. Unfortunately, the patient continued to deteriorate, requiring implantation of a Berlin Heart LVAD that was approved by the Food and Drug Administration on terms of "Compassionate Use." A 30-mL LVAD was subsequently placed in series (left ventricular apex to aorta) and the patient remained without anticoagulation for the first postoperative day. A mediastinal reexploration for hematoma removal was required the following day, with the patient subsequently administered IV heparin to maintain the activated partial thromboplastin time between 50–70 s as previously described (3) until postoperative day 13. Warfarin therapy was commenced on postoperative day 3, with coadministration of aspirin 20 mg per day advanced to twice a day by postoperative day 7. The intended international normalized ratio (INR) was 2.5–3.5 with continuous warfarin administration as previously described (4). Dipyridamole 20 mg twice a day was added to the anticoagulation regimen on postoperative day 6. Lastly, in response to detection of aspirin resistance with Platelet Mapping® (Hemoscope, Niles, IL), clopidogrel 25 mg per day was administered on postoperative day 11. After clopidogrel administration, the patient subsequently demonstrated adequate platelet sensitivity (85%–95%) to both aspirin and clopidogrel during LVAD therapy. With the exception of warfarin administration, which was modified to maintain target INR values, anticoagulant therapy was continued without change before transplantation 6 wk after LVAD placement.
Standard coagulation parameters were generated by our cardiothoracic intensive care unit laboratory. Thrombelastographic data were obtained from blood collected into 3.2% sodium citrate containing plastic tubes. Both whole blood and plasma (obtained by 15 min centrifugation at 3000g) were activated (1 mL into a standard, kaolin-containing vial) before being placed in a computer-controlled thrombelastograph® (TEG®) hemostasis system (Model 5000, Hemoscope, Niles, IL), with addition of CaCl2 as the last step to initiate clotting. Heparinase was used when heparin was administered. TEG data were collected with Version 4.2 software, with both traditional variables and newer, parametric variables. Figure 1 displays changes in clot strength, fibrinogen concentration and platelet count. After postoperative day 1, whole blood clot strength rapidly returned to normal, and by postoperative day 12 and thereafter, it exceeded the 95th percentile of the institutional normal range. Hyperfibrinogenemia was observed by postoperative day 3, and thrombocytosis was noted on postoperative day 7. INR values met or exceeded target values (Fig. 2), with variability attributed to changes inpatient tolerance of oral and/or enteral tube nutrition. With regard to clot kinetics (Fig. 2), clot initiation was rapidly restored after LVAD placement, becoming prolonged after warfarin administration. The speed of clot propagation rapidly increased into the normal range and subsequently remained above average. A detailed analysis with clot growth velocity curves (Fig. 3) demonstrated that plasma-based coagulation rapidly recovered within the first week after LVAD placement, which was in time attenuated with warfarin. This is of particular interest, in that the first derivative of clot growth determined by TEG is significantly correlated with thrombin generation as measured by thrombin– antithrombin complex concentration change (7). During this early period, platelet function was compromised. However, by the second postoperative week, platelet-mediated effects on hemostasis predominated, with clot speed and strength was twofold of normal values.
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Figure 1. Hemostatic course after implantation of a Berlin Heart; clot strength end points. Berlin Heart implantation was associated with a rapid increase in clot strength. Fibrinogen concentrations increased to abnormally great values within 3 days and platelet count reached abnormally great values within a week of implantation. MG = maximum elastic modulus; MA = maximum amplitude. Hatched gray bar represents institutional 95% confidence intervals.
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Figure 2. Hemostatic course after implantation of a Berlin Heart; clot initiation and propagation end points. Berlin Heart implantation was associated with a rapid decrease in time to clot initiation that was attenuated with warfarin. Clot propagation also rapidly reached abnormally great values within a week after Berlin Heart placement. INR = international normalized ratio; r = reaction time (a measure of clot initiation); angle = a measure of clot propagation; MRTG = maximum rate of thrombus generation, a measure of clot propagation. Hatched gray bar represents therapeutic target range for warfarin therapy in the graphic displaying INR data. Hatched gray bar represents institutional 95% confidence intervals within the remaining graphics.
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Figure 3. Representative clot growth velocity curves of the first 2 wk after implantation of a Berlin Heart. Immediately after Berlin Heart placement, the velocity of clot growth was markedly depressed. However, within one day the plasmatic portion of coagulation rapidly recovered, but with evidence of diminished platelet function. While platelet function continued to return 6 days after Berlin Heart placement, the contribution of platelet activation as the predominant hemostatic force occurred 14 days after Berlin Heart placement, persisting for the weeks preceding heart transplantation. Black curve = whole blood, gray curve = plasma.
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The patient had heart transplantation after 6 wk of LVAD therapy, with a significant coagulopathy encountered after protamine administration. The patient was administered 30 mL/kg of platelets, 59 mL/kg fresh frozen plasma, 6 mL/kg cryoprecipitate, and 33 mL/kg packed red blood cells; however, bleeding finally ceased after administration of 25 µg/kg of activated Factor VII based on TEG data, suggestive of a persistent coagulation factor deficiency based on prolonged R and subnormal angle values. Of interest, the LVAD had no sign of fibrin/clot accumulation. The patient was discharged home 2 wk after transplantation without complication.
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DISCUSSION
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The principle finding of this case was that a rapid, prolonged hypercoagulable systemic response to LVAD placement evolves, with a predominantly protein-mediated component in the first few days followed by a delayed, but far greater, platelet-mediated component. Without aggressive, multimodal anticoagulant therapy, our findings indicate that device thrombosis/ thromboembolism and consequent patient morbidity would likely occur. Second, once anticoagulant therapy is maximized, significant coagulopathy should be anticipated during any surgical intervention, potentially requiring extraordinary intervention as with this patient during heart transplantation. The extraordinary transfusion requirements of adult patients with mechanical circulatory support devices undergoing transplantation are similar to those encountered with our patient (8). In summary, when proscribing anesthetic and surgical management of patients with a Berlin Heart, consideration of hypercoagulable features and anticoagulant therapy must be made to maximize patient safety.
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Footnotes
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Accepted for publication November 5, 2006.
Supported by the Departments of Anesthesiology and Surgery.
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REFERENCES
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- Ishino K, Loebe M, Uhlemann F, et al. Circulatory support with paracorporeal pneumatic ventricular assist device (VAD) in infants and children. Eur J Cardio-Thorac Surg 1997;11:965–72.[Abstract]
- Hetzer R, Loebe M, Potapov EV, et al. Circulatory support with pneumatic paracorporeal ventricular assist device in infants and children. Ann Thorac Surg 1998;66:1498–506.[Abstract/Free Full Text]
- Stiller B, Weng Y, Hubler M, et al. Pneumatic pulsatile ventricular assist devices in children under 1 year of age. Eur J Cardio-Thorac Surg 2005;28:234–9.[Abstract/Free Full Text]
- Arabia FA, Tsau PH, Smith RG, et al. Pediatric bridge to heart transplantation: application of the Berlin heart, Medos and Thoratec ventricular assist devices. J Heart Lung Transplant 2006;25:16–21.[ISI][Medline]
- Dunnington GH, Sleasman J, Alkhaldi A, et al. Successful bridge to transplant using the Berlin heart left ventricular assist device in a 3-month-old infant. Ann Thorac Surg 2006;81:1116–8.[Abstract/Free Full Text]
- Lazar RM, Shapiro PA, Jaski BE, et al. Neurological events during long-term mechanical circulatory support for heart failure. Circulation 2004;109:2423–7.[Abstract/Free Full Text]
- Rivard GE, Brummel-Ziedins KE, Mann KG, et al. Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography. J Thromb Haemost 2005;3:2039–43.[ISI][Medline]
- Wegner JA, DiNardo JA, Arabia FA, Copeland JG. Blood loss and transfusion requirements in patients implanted with a mechanical circulatory support device undergoing cardiac transplantation. J Heart Lung Transplant 2000;19:504–6.[ISI][Medline]
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Abstract
Introduction
