Ann Thorac Cardiovasc Surg Advance Published Date: January 15, 2016
doi: 10.5761/atcs.cr.15-00345
Case Report
Heparin-Induced-Thrombocytopenia Causing Massive Aortic Thrombosis after Ascending Aortic Replacement for Type A Acute Aortic Dissection Yusuke Matsuki, MD,1 Kiyotaka Imoto, MD,1 Keiji Uchida, MD,1 Susumu Isoda, MD,1 Norihisa Karube, MD,1 Shota Yasuda, MD,1 and Munetaka Masuda, MD2
A 77-year-old woman underwent emergency ascending aortic replacement for type A acute aortic dissection. Fifteen days after the operation, she had motor and sensory disturbances in the lower limbs. Computed tomography revealed multiple aortic thrombi and disrupted blood flow in the right external iliac and left common iliac arteries. She underwent an emergency thrombectomy for acute limb ischemia. Because heparininduced-thrombocytopenia (HIT) was suspected to have caused the multiple aortic thrombi, we postoperatively changed the anticoagulant therapy from heparin to argatroban. Seventeen days after the first operation, gastrointestinal bleeding developed, and the patient died of mesenteric ischemia caused by HIT. Arterial embolization caused by HIT after cardiovascular surgery is a rare, but fatal event. To avoid fatal complications, early diagnosis and early treatment are essential. Use of a scoring system would probably facilitate early diagnosis. Keywords: HIT, acute type A dissection, aortic thrombosis, heparin
Introduction
Case Presentation
Heparin-induced thrombocytopenia (HIT) after cardiovascular surgery has recently been reported in Japan, and this condition must be included in the differential diagnosis when the platelet count decreases in association with heparin administration. We describe our experience with a patient in whom HIT caused massive aortic thrombosis after surgery for acute type A aortic dissection.
A 77-year-old woman complained of sudden chest pain and was admitted to the emergency department in shock. We diagnosed acute type A aortic dissection and cardiac tamponade on contrast-enhanced computed tomography (CT) and ultrasonography. Emergency operation was performed. We found the entry tear in the ascending aorta and performed ascending aortic replacement. During the operation, 45000 unit of heparin was administered, which was the first time for her. The extracorporeal circulation time was 148 min, the cardiac arrest time was 99 min, and the lower-body circulatory arrest time was 41 min. The patient was admitted to the intensive care unit (ICU) after the operation. Because mechanical ventilation had been prolonged by respiratory dysfunction, heparinization was begun to prevent deep venous thrombosis (DVT) on postoperative day (POD) 4. She was extubated on POD 7. The patient recovered uneventfully and could
Cardiovascular Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan 2Department of Surgery, Cardiovascular Surgery, Yokohama City University, Yokohama, Kanagawa, Japan 1
Received: November 19, 2015; Accepted: December 18, 2015 Corresponding author: Yusuke Matsuki, MD. Department of Cardiovascular Surgery, Fujisawa City Hospital, 2-6-1 Fujisawa, Fujisawa City, Kanagawa 251-8550, Japan Email: [email protected] ©2016 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved.
1
Ann Thorac Cardiovasc Surg Advance Published Date: January 15, 2016 Matsuki Y, et al. (A)
(C)
(D)
(B)
Fig. 1 C ontrast-enhanced CT scans showing multiple aortic thrombi in the distal anastomosis (A), aortic root (B), and prosthetic graft (C). Blood flow disruption in the right external iliac artery and left common iliac artery was detected on 3-dimensional CT angiography (D). CT: computed tomography
2
Heparin
argatroban
Plt ×104/µl
have meals and walk unaided. Heparinization was therefore stopped on POD 13. On stopping the administration of heparin, rest pain of the lower limbs developed. On POD 15, the patient had motor and sensory disturbances in the lower limbs. Arterial Doppler flow was not detected in either leg, and laboratory examinations showed rapid increase in the creatinine kinase (2358 U/L) and lactate dehydrogenase (485 U/L) levels. A CT scan showed multiple aortic thrombi at the aortic root, distal anastomosis, and in the graft (Fig. 1). CT scanning also revealed disrupted blood flow in the right external iliac and left common iliac arteries. She underwent an emergency thrombectomy. Because 8 h had elapsed since the emergence of ischemia, and there was the risk of myonephropathic metabolic syndrome (MNMS), we started continuous hemodiafiltration before thrombectomy. Most thrombi were fresh blood clots, but some white clots were found in the fresh thrombi. We performed fasciotomy of right lower limb postoperatively because the right calf had become turgescent, and the muscle division pressure had increased to 50 mmHg. Because the platelet count decreased after 7 days of heparin therapy (Fig. 2), and multiple thrombi were present, we suspected HIT. Before thrombectomy, we performed tests for antibodies that could cause coagulation disorders, including HIT antibodies. After surgery, we changed all arterial-line fluids, and switched the anticoagulant therapy from heparin to argatroban.
4T’s score=6 point ICU 䋷POD
Postoperative day (POD)
15POD motor and sensory disturbance of the lower limbs
Fig. 2 T ime course of the platelet count and anticoagulant therapy. The platelet count decreased from POD 7. The patient had movement and sensory disorders of the lower limbs on POD 15. We performed thrombectomy of the lower limbs and changed anticoagulant therapy from heparin to argatroban. POD: postoperative day; ICU: intensive care unit
The blood flow of the lower limbs improved, and the vital signs were stable. On POD 17, there was bloody drainage from a gastric tube, and hematochezia developed. Metabolic acidosis progressed rapidly, and blood pressure decreased. It was suspected that mesenteric ischemia had developed. Finally, the patient died on POD 18. The HIT antibody was positive, and there were no findings of congenital coagulation disorders such as antiphospholipid antibody syndrome or protein C deficiency. We considered HIT to be related to the cause of death.
Ann Thorac Cardiovasc Surg Advance Published Date: January 15, 2016 HIT-Induced Aortic Thrombosis after Surgery for AAD Type A
Fig. 3 4 T’s score6) for the clinical diagnosis of HIT. This score consists of four categories: Thrombocytopenia, Timing of platelet count fall, Thrombosis or other sequelae, and other cause of thrombocytopenia not evident. The total score is then calculated, and if the 4T’s score is 4 or higher, immediate therapy for HIT is recommended. *Timing of clinical sequelae, such as thrombocytopenia, thrombosis, or skin lesions. **Two points if necrotizing heparininduced skin lesions even if thrombocytopenia not present. DIC: disseminated intravascular coagulation; HIT: heparin-induced thrombocytopenia; LMWH: low-molecular weight heparin; DTH: delayed-type hypersensitivity
Discussion Walls et al. reported that the incidence of HIT after open-heart surgery is 1.9%, indicating that HIT is very rare.1) The measurement of anti-PF4/heparin antibodies or HIT antibodies on enzyme-linked immunosorbent assay (ELISA) is often performed for the serologic diagnosis of HIT. However, care must be exercised in the diagnosis HIT, because the rate of positivity for HIT antibodies after cardiac surgery ranges from 27% to 50%,2) and ELISA-based tests have relatively poor specificity. Furthermore, because the measurement of HIT antibody concentrations takes a prolonged time, an early diagnosis should be made on the basis of clinical signs and symptoms to facilitate early treatment. In recent years, clinical scoring systems have been used for diagnosis of HIT. The 4T’s score3) (Fig. 3) is a
well-known scoring system which is based on four clinical features: (1) the magnitude of thrombocytopenia; (2) the timing of thrombocytopenia or thrombosis or other clinical sequelae in relation to the initiation of a course of heparin; (3) the presence of thrombosis (or other clinical sequelae), and (4) the presence of other potential non-HIT explanations for thrombocytopenia or other clinical events. We determine the score for each category and diagnose HIT on the basis of the total score. The sensitivity and specificity of the 4T’s score at a cut-off value of ≥4 are 0.99 (0.86–1.00) and 0.54 (0.43–0.66), respectively. When the cut-off value of the 4T’s score is more than 6 points, the probability of HIT is higher than 80%.3) The HIT Expert Probability (HEP) score4) is another scoring system that has been developed to facilitate the early clinical diagnosis and rapid treatment of HIT.
3
Ann Thorac Cardiovasc Surg Advance Published Date: January 15, 2016 Matsuki Y, et al.
In our patient, the platelet count began to decrease 7 days after the first emergency operation with heparin administration. The platelet count decreased by more than 50% (from 23 × 104/µL to 7 × 104/µL). Acute limb ischemia developed after the first operation. On the basis of these findings, the 4T’s score was 6 points, indicating a very high likelihood of HIT in our patient. However, we could not diagnose HIT until acute arterial embolism occurred. One cause of delayed diagnosis is that thrombocytopenia is an extremely common finding after open-heart surgery. The platelet count decreases after open-heart surgery with cardiopulmonary bypass owing to the adsorption and mechanical destruction of platelets in the cardiopulmonary bypass circuit, in conjunction with the loss of platelets due to operative bleeding.5) We thought that thrombocytopenia had been caused by these reasons after operation, which delayed our suspicion of HIT. The incidence of arterial embolism in HIT is rather low, ranging from 3% to 10%, whereas that of venous thrombosis is 17% to 55%.6) However, arterial embolism is fatal. Walls et al. reported that mesenteric thrombosis occurred in 3 of 70 patients who underwent open-heart surgery, all of whom died. Twelve patients had gastrointestinal bleeding, and 5 (42%) of these patients died.1) The development of gastrointestinal complications, particularly mesenteric thrombosis, in patients with HIT has fatal consequences, similar to our patient. Massive arterial thrombosis was detected on CT scans in our patient, but some cases in which organ ischemia progresses in the absence of arteriovenous thrombi have been reported.7) To prevent fatal complications of HIT, a scoring system for the diagnosis of HIT should be used to evaluate patients who have thrombocytopenia while receiving heparin 5 days after surgery. Patients who have a score of four or higher should start to receive treatment for HIT.
Conclusion We described our experience with a patient in whom HIT caused massive aortic thrombosis after surgery for
4
acute type A aortic dissection, leading to lower limb ischemia and fatal mesenteric embolism. If thrombocytopenia rapidly develops 5 days after open-heart surgery with heparin administration, HIT should be strongly suspected and evaluated with the use of a scoring system to facilitate the early diagnosis and treatment of HIT and thereby avoid fatal complications.
Disclosure Statement The authors have no conflict of interest to declare.
References 1) Walls JT, Curtis JJ, Silver D, et al. Heparin-induced thrombocytopenia in open heart surgical patients: sequelae of late recognition. Ann Thorac Surg 1992; 53: 787-91. 2) Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 2003; 76: 2121-31. 3) Cuker A, Gimotty PA, Crowther MA, et al. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and metaanalysis. Blood 2012; 120: 4160-7. 4) Cuker A, Arepally G, Crowther MA, et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost 2010; 8: 2642-50. 5) Atsutomo M, Kouzou K, Yuichi Y, et al. A case of heparin-induced thrombocytopenia (HIT) with postoperative cerebral infarction following surgical repair of acute type A aortic dissection. Jpn J Cardiovasc Surg 2010; 39: 17-20. 6) Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e495S-530S. 7) Masayoshi K, Yoshiharu T, Kenji M, et al. A case of heparin-induced thrombocytopenia (HIT) following aortic surgery for acute type A aortic dissection. Jpn J Cardiovasc Surg 2006; 35: 222-5.
doi: 10.5761/atcs.cr.15-00345
Case Report
Heparin-Induced-Thrombocytopenia Causing Massive Aortic Thrombosis after Ascending Aortic Replacement for Type A Acute Aortic Dissection Yusuke Matsuki, MD,1 Kiyotaka Imoto, MD,1 Keiji Uchida, MD,1 Susumu Isoda, MD,1 Norihisa Karube, MD,1 Shota Yasuda, MD,1 and Munetaka Masuda, MD2
A 77-year-old woman underwent emergency ascending aortic replacement for type A acute aortic dissection. Fifteen days after the operation, she had motor and sensory disturbances in the lower limbs. Computed tomography revealed multiple aortic thrombi and disrupted blood flow in the right external iliac and left common iliac arteries. She underwent an emergency thrombectomy for acute limb ischemia. Because heparininduced-thrombocytopenia (HIT) was suspected to have caused the multiple aortic thrombi, we postoperatively changed the anticoagulant therapy from heparin to argatroban. Seventeen days after the first operation, gastrointestinal bleeding developed, and the patient died of mesenteric ischemia caused by HIT. Arterial embolization caused by HIT after cardiovascular surgery is a rare, but fatal event. To avoid fatal complications, early diagnosis and early treatment are essential. Use of a scoring system would probably facilitate early diagnosis. Keywords: HIT, acute type A dissection, aortic thrombosis, heparin
Introduction
Case Presentation
Heparin-induced thrombocytopenia (HIT) after cardiovascular surgery has recently been reported in Japan, and this condition must be included in the differential diagnosis when the platelet count decreases in association with heparin administration. We describe our experience with a patient in whom HIT caused massive aortic thrombosis after surgery for acute type A aortic dissection.
A 77-year-old woman complained of sudden chest pain and was admitted to the emergency department in shock. We diagnosed acute type A aortic dissection and cardiac tamponade on contrast-enhanced computed tomography (CT) and ultrasonography. Emergency operation was performed. We found the entry tear in the ascending aorta and performed ascending aortic replacement. During the operation, 45000 unit of heparin was administered, which was the first time for her. The extracorporeal circulation time was 148 min, the cardiac arrest time was 99 min, and the lower-body circulatory arrest time was 41 min. The patient was admitted to the intensive care unit (ICU) after the operation. Because mechanical ventilation had been prolonged by respiratory dysfunction, heparinization was begun to prevent deep venous thrombosis (DVT) on postoperative day (POD) 4. She was extubated on POD 7. The patient recovered uneventfully and could
Cardiovascular Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan 2Department of Surgery, Cardiovascular Surgery, Yokohama City University, Yokohama, Kanagawa, Japan 1
Received: November 19, 2015; Accepted: December 18, 2015 Corresponding author: Yusuke Matsuki, MD. Department of Cardiovascular Surgery, Fujisawa City Hospital, 2-6-1 Fujisawa, Fujisawa City, Kanagawa 251-8550, Japan Email: [email protected] ©2016 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved.
1
Ann Thorac Cardiovasc Surg Advance Published Date: January 15, 2016 Matsuki Y, et al. (A)
(C)
(D)
(B)
Fig. 1 C ontrast-enhanced CT scans showing multiple aortic thrombi in the distal anastomosis (A), aortic root (B), and prosthetic graft (C). Blood flow disruption in the right external iliac artery and left common iliac artery was detected on 3-dimensional CT angiography (D). CT: computed tomography
2
Heparin
argatroban
Plt ×104/µl
have meals and walk unaided. Heparinization was therefore stopped on POD 13. On stopping the administration of heparin, rest pain of the lower limbs developed. On POD 15, the patient had motor and sensory disturbances in the lower limbs. Arterial Doppler flow was not detected in either leg, and laboratory examinations showed rapid increase in the creatinine kinase (2358 U/L) and lactate dehydrogenase (485 U/L) levels. A CT scan showed multiple aortic thrombi at the aortic root, distal anastomosis, and in the graft (Fig. 1). CT scanning also revealed disrupted blood flow in the right external iliac and left common iliac arteries. She underwent an emergency thrombectomy. Because 8 h had elapsed since the emergence of ischemia, and there was the risk of myonephropathic metabolic syndrome (MNMS), we started continuous hemodiafiltration before thrombectomy. Most thrombi were fresh blood clots, but some white clots were found in the fresh thrombi. We performed fasciotomy of right lower limb postoperatively because the right calf had become turgescent, and the muscle division pressure had increased to 50 mmHg. Because the platelet count decreased after 7 days of heparin therapy (Fig. 2), and multiple thrombi were present, we suspected HIT. Before thrombectomy, we performed tests for antibodies that could cause coagulation disorders, including HIT antibodies. After surgery, we changed all arterial-line fluids, and switched the anticoagulant therapy from heparin to argatroban.
4T’s score=6 point ICU 䋷POD
Postoperative day (POD)
15POD motor and sensory disturbance of the lower limbs
Fig. 2 T ime course of the platelet count and anticoagulant therapy. The platelet count decreased from POD 7. The patient had movement and sensory disorders of the lower limbs on POD 15. We performed thrombectomy of the lower limbs and changed anticoagulant therapy from heparin to argatroban. POD: postoperative day; ICU: intensive care unit
The blood flow of the lower limbs improved, and the vital signs were stable. On POD 17, there was bloody drainage from a gastric tube, and hematochezia developed. Metabolic acidosis progressed rapidly, and blood pressure decreased. It was suspected that mesenteric ischemia had developed. Finally, the patient died on POD 18. The HIT antibody was positive, and there were no findings of congenital coagulation disorders such as antiphospholipid antibody syndrome or protein C deficiency. We considered HIT to be related to the cause of death.
Ann Thorac Cardiovasc Surg Advance Published Date: January 15, 2016 HIT-Induced Aortic Thrombosis after Surgery for AAD Type A
Fig. 3 4 T’s score6) for the clinical diagnosis of HIT. This score consists of four categories: Thrombocytopenia, Timing of platelet count fall, Thrombosis or other sequelae, and other cause of thrombocytopenia not evident. The total score is then calculated, and if the 4T’s score is 4 or higher, immediate therapy for HIT is recommended. *Timing of clinical sequelae, such as thrombocytopenia, thrombosis, or skin lesions. **Two points if necrotizing heparininduced skin lesions even if thrombocytopenia not present. DIC: disseminated intravascular coagulation; HIT: heparin-induced thrombocytopenia; LMWH: low-molecular weight heparin; DTH: delayed-type hypersensitivity
Discussion Walls et al. reported that the incidence of HIT after open-heart surgery is 1.9%, indicating that HIT is very rare.1) The measurement of anti-PF4/heparin antibodies or HIT antibodies on enzyme-linked immunosorbent assay (ELISA) is often performed for the serologic diagnosis of HIT. However, care must be exercised in the diagnosis HIT, because the rate of positivity for HIT antibodies after cardiac surgery ranges from 27% to 50%,2) and ELISA-based tests have relatively poor specificity. Furthermore, because the measurement of HIT antibody concentrations takes a prolonged time, an early diagnosis should be made on the basis of clinical signs and symptoms to facilitate early treatment. In recent years, clinical scoring systems have been used for diagnosis of HIT. The 4T’s score3) (Fig. 3) is a
well-known scoring system which is based on four clinical features: (1) the magnitude of thrombocytopenia; (2) the timing of thrombocytopenia or thrombosis or other clinical sequelae in relation to the initiation of a course of heparin; (3) the presence of thrombosis (or other clinical sequelae), and (4) the presence of other potential non-HIT explanations for thrombocytopenia or other clinical events. We determine the score for each category and diagnose HIT on the basis of the total score. The sensitivity and specificity of the 4T’s score at a cut-off value of ≥4 are 0.99 (0.86–1.00) and 0.54 (0.43–0.66), respectively. When the cut-off value of the 4T’s score is more than 6 points, the probability of HIT is higher than 80%.3) The HIT Expert Probability (HEP) score4) is another scoring system that has been developed to facilitate the early clinical diagnosis and rapid treatment of HIT.
3
Ann Thorac Cardiovasc Surg Advance Published Date: January 15, 2016 Matsuki Y, et al.
In our patient, the platelet count began to decrease 7 days after the first emergency operation with heparin administration. The platelet count decreased by more than 50% (from 23 × 104/µL to 7 × 104/µL). Acute limb ischemia developed after the first operation. On the basis of these findings, the 4T’s score was 6 points, indicating a very high likelihood of HIT in our patient. However, we could not diagnose HIT until acute arterial embolism occurred. One cause of delayed diagnosis is that thrombocytopenia is an extremely common finding after open-heart surgery. The platelet count decreases after open-heart surgery with cardiopulmonary bypass owing to the adsorption and mechanical destruction of platelets in the cardiopulmonary bypass circuit, in conjunction with the loss of platelets due to operative bleeding.5) We thought that thrombocytopenia had been caused by these reasons after operation, which delayed our suspicion of HIT. The incidence of arterial embolism in HIT is rather low, ranging from 3% to 10%, whereas that of venous thrombosis is 17% to 55%.6) However, arterial embolism is fatal. Walls et al. reported that mesenteric thrombosis occurred in 3 of 70 patients who underwent open-heart surgery, all of whom died. Twelve patients had gastrointestinal bleeding, and 5 (42%) of these patients died.1) The development of gastrointestinal complications, particularly mesenteric thrombosis, in patients with HIT has fatal consequences, similar to our patient. Massive arterial thrombosis was detected on CT scans in our patient, but some cases in which organ ischemia progresses in the absence of arteriovenous thrombi have been reported.7) To prevent fatal complications of HIT, a scoring system for the diagnosis of HIT should be used to evaluate patients who have thrombocytopenia while receiving heparin 5 days after surgery. Patients who have a score of four or higher should start to receive treatment for HIT.
Conclusion We described our experience with a patient in whom HIT caused massive aortic thrombosis after surgery for
4
acute type A aortic dissection, leading to lower limb ischemia and fatal mesenteric embolism. If thrombocytopenia rapidly develops 5 days after open-heart surgery with heparin administration, HIT should be strongly suspected and evaluated with the use of a scoring system to facilitate the early diagnosis and treatment of HIT and thereby avoid fatal complications.
Disclosure Statement The authors have no conflict of interest to declare.
References 1) Walls JT, Curtis JJ, Silver D, et al. Heparin-induced thrombocytopenia in open heart surgical patients: sequelae of late recognition. Ann Thorac Surg 1992; 53: 787-91. 2) Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 2003; 76: 2121-31. 3) Cuker A, Gimotty PA, Crowther MA, et al. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and metaanalysis. Blood 2012; 120: 4160-7. 4) Cuker A, Arepally G, Crowther MA, et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost 2010; 8: 2642-50. 5) Atsutomo M, Kouzou K, Yuichi Y, et al. A case of heparin-induced thrombocytopenia (HIT) with postoperative cerebral infarction following surgical repair of acute type A aortic dissection. Jpn J Cardiovasc Surg 2010; 39: 17-20. 6) Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e495S-530S. 7) Masayoshi K, Yoshiharu T, Kenji M, et al. A case of heparin-induced thrombocytopenia (HIT) following aortic surgery for acute type A aortic dissection. Jpn J Cardiovasc Surg 2006; 35: 222-5.
