Case Report A 61-year-old Man with Disseminated Intravascular Coagulation: A Case Report Markus U. Wagenh€ auser,1 Neshlian Ertas,1 Tolga A. Sagban,1 Mareike Witte,1 Till Hoffman,2 1 Hubert Schelzig, and Alexander Oberhuber,1 D€ ussedorf, Germany
Background: Disseminated intravascular coagulation (DIC) can frequently be observed in patients with severe inflammatory response. It is still correlated with a poor prognosis. Activation of coagulation activity leads to occlusions of small vessels resulting in various organ failure symptoms. In addition, secondary fibrinolysis leads to an increased risk of bleedings and means a therapeutic dilemma. Here, we present a case of a 61-year-old Caucasian man with a severe case of DIC and its clinical complications. Methods: We report the case of a man with a severe case of DIC. Data collection was performed retrospectively. Results: We report the case of a 61-year-old Caucasian man with contact to pigeon droppings in his medical history. This was followed by a rhinopharyngitis, an exanthema, and a recurring priapism. Thrombotic occlusions were predominant on admission, and necrosis of the lower legs, the hands, and the genital resulted in amputation. Hypoperfusion of the rectum and the bladder lead to the creation of a descendostoma and an uretrostoma. Anticoagulation was managed by continuous infusion of unfractionated heparin and activated protein C supplementation. Long-term anticoagulation is managed with rivaroxaban. Conclusions: Cryptococcus soil inhalation may cause severe DIC resulting in extremity amputations; however, effective anticoagulation and activated protein C supplementation might extenuate the progress. As multiple complications might occur, an interdisciplinary cooperation is essential.
In 1772, Hewson1 first described observations that in intense bleeding patients the blood occurring the last clotted earlier than the blood occurring fist. This finding could be repeatedly observed in trauma patients and patients with severe systemic inflammatory response, presumably because of acidosis and high catecholamine levels.2 A widely used synonym for disseminated intravascular coagulation (DIC) is 1 Department of Vascular and Endovascular Surgery, University Hospital D€ usseldorf, D€ ussedorf, Germany. 2 Department of Hemostaseology, University Hospital D€ usseldorf, D€ ussedorf, Germany.
Correspondence to: Markus U. Wagenh€auser, Department of Vascular and Endovascular Surgery, Moorenstrasse 5, 40225 D€ usseldorf, Germany; E-mail: markus.wagenhaeuser@med. uni-duesseldorf.de Ann Vasc Surg 2014; -: 1–6 http://dx.doi.org/10.1016/j.avsg.2014.01.024 Ó 2014 Elsevier Inc. All rights reserved. Manuscript received: September 13, 2013; manuscript accepted: January 14, 2014; published online: ---.
the expression ‘‘death is coming’’3 and demonstrates the severity of the diagnosis. To start the cascade of intravascular clotting, a stimulus needs to be introduced into the organism. The mechanism of introduction and the application rate may be responsible for clinical severity of symptoms.4 There is no laboratory test available to give evidence to the diagnosis of DIC. Low platelet count 30 mm Hg. Inguinal, femoral, and popliteal pulses were palpable bilaterally; however, peripheral pulses were missing. Both feet were acute ischemic, and computed tomography (CT) scans showed a total bilateral and arterial occlusion in the middle of the lower leg with intramuscular hemorrhages and muscular swelling. In addition, mild-hemorrhagic freeabdominal liquid (perihepatic, perisplenic, and retroperitoneal) without signs of an active bleeding could be seen on CT scans. Representative radiologic findings and results of the first blood examinations after admission are shown in Figure 1. Immediate fasciotomy was performed, thrombotic occlusion of the small veins of the lower legs could be observed. Intraoperative angiography showed ruptures of small arteries and bleedings of the anterior tibial artery, explaining the CT scan findings. Skin closure was not possible, so temporarily a negative-pressure wound therapy at both lower legs was initiated. Because of acute
Annals of Vascular Surgery
ischemia of the genitals, the Department of Urology participated in the operation and could find a thrombotic occlusion of the small intracorporal veins; thus, a decompressive punctuation was not possible anymore. The patient was transferred to the intensive care unit. There was no evidence of an endocarditis according to a transthoracic echocardiogram, neither of an immunologicrelated disease according to blood examination results. Thrombotic affinity was predominant, and there was no clinical sign of active bleeding. The coagulative management was arranged in an interdisciplinary consent between the Department of Hemostaseology, the physicians in charge of the intensive care unit, and the Department of Vascular Surgery. As protein C showed a reduced level of activity in the initial blood test results, we substituted a total of 10,000 international units (I.E) Ceprotin (zymogen protein C). The first dose was 70 I.E./kg and the following doses were substituted appropriate to the regularly monitored (every 6 hr) activity level of protein C. In the further course, we started effective anticoagulation by continuous infusion of unfractionated heparin (UFH). The therapeutic range was an aPTT of 50e70 sec. Thus, the mean dose of UFH was about 270 I.E./kg/day. Several attempts to reduce effective anticoagulation (aPPT monitored) and to stop continuous infusion of UFH resulted in increased levels of D-dimers, thus anticoagulation could not be reduced. The patient’s received several red blood cell and plasma transfusions. Moreover, he also received 4 platelet concentrates transfusions. In general, we accepted moderate supressed levels of procoagulative factors as thrombotic affinity was clinically predominant in the absence of any bleeding signs in the further course. The transfusion of purified factors other than zymogen protein C was not necessary. Necrosis of the lower legs proceeded up to the popliteal fossa with progressive muscle necrosis. Necrosis of the hands proceeded up to wrists and necrosis of the genital and anal area were also progressive (Fig. 2). Leg preservation was not possible, and above-knee amputation was performed after complete demarcation. We had to perform amputation of both the hands, the scrotum, and a part of the penis. In the middle of April, the patient showed acute abdominal pain. We conducted an immediate CT scan that showed perihepatic free air and an ischemia of the rectum. Moreover, acute hydronephrosis grade IIe III could be observed. Main findings are shown in Figure 3. Exploratory laparatomy was performed and ended with rectum extirpation and descendostoma creation. The bladder showed regional sign of hypoperfusion; however, there was no indication for resection. Therefore, transurethral splinting of the ureter and protective uretrostoma had to be performed because of consistent hypoperfusion. Hemoglobin decline could be seen twice, so that the patient had to undergo relaparatomy twice. Here, we could find diffusive bleeding, so we performed hematoma removal and attended the accompanying abdominal compartment with an open abdomen and vicryl mesh covering.
Vol.
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No.
-, -
2014
Case Report 3
Fig. 1. Results of the first blood test and representative findings of the first CT scan after admission. Here, results important for the ISTH Diagnostic Scoring System for DIC are presented. (A) Three arteries of the upper part of the lower leg with correct contrast after contrast agent application, demonstrating regular perfusion. (B) No arterial flow can be seen in the middle part of the lower leg after
contrast agent application. A sudden break off of the arterial flow accompanied with muscles swelling could be observed because of arterial occlusion and presented clinically as acute compartment syndrome. (C) Lower pelvis with mild-hemorrhagic free-abdominal liquid (*). No active bleeding could be found.
As the closure of the laparastoma was not possible, we had to await secondary wound healing and could close the laparastoma eventually using a mesh graft from the upper left leg. Screening blood tests, which were done shortly after admission, rejected the suspicion of a rheumatologicrelated disease. Moreover, these blood tests could not prove a subliminal Cryptococcus infection. However, we treated the patient with Amphotericin B at a dose of 1 mg/kg a day for 14 days altogether, knowing that subliminal infections do not always show positive blood test results. Therefore, the effectiveness of the antimycotic therapy remains uncertain. The results of the hematologic blood tests showed the expression of wild-type factor V Leiden and prothrombin. Activated protein C (APC) resistance and heparininduced thrombocytopenia type II could be excluded, and von Willebrand factor showed normal level of activity. The clotting factors II, VII, IX, X, and XIII showed minimally supressed levels of activity, so that the patient did not need coagulation factor replacement therapy. The general condition of the patient improved. A transfer to the ward was possible and performed in the middle of July. Changes of the wound dressings could be performed on the ward. We also supplied a drinking bottle retainer and special bell to increase the patient’s satisfaction and well-being. To achieve an acceptable level of autonomy, alignment of exoprothesis is initiated and an
appointment for rehabilitation has been arranged. Again, the agreement to start rivaroxaban medication as longterm effective anticoagulation has been arranged interdisciplinary.
DISCUSSION We presented a case of severe DIC with many clinical complications resulting in amputation of extremity parts because of vascular occlusions. DIC is a complex and acquired syndrome with activated intravascular coagulation resulting in fibrin formation depositing predominantly in small vessels. As a result, fibrinolysis is activated increasing the risk of bleeding.11,12 Although DIC often occurs in combination with severe sepsis,13 other agents might also be responsible. Our patient’s medical history outlines that he had contact to pigeon droppings 6 weeks before hospital admission. It is known that Cryptococcus can frequently be found in pigeon droppings. It is an encapsulated yeast-like fungus that may cause severe pulmonary and neurologic diseases after contaminated soil inhalation.14,15 Generally, Cryptococcus infections lead to meningitis, pulmonary
4 Case Report
Annals of Vascular Surgery
Fig. 2. Representative pictures of main clinical findings before amputation. (A) Livid discoloration and necrosis up to the middle part of both lower legs. (B) Livid discoloration and necrosis of the left hand marginal above the wrist. The right hand showed equal findings. (C)
Presentation after fasciotomy and application of negative-pressure wound therapy. Both knees showed extensive subcutaneous hemorrhages. (D) Livid discoloration and necrosis of genital. Clinical presentation showed progress and demarcation during hospital stay.
infiltrates, and skin lesions.16,17 Thus, the exanthema might also be a sign of Cryptococcus infection. In our patient, we hypothesized that mild subliminal forms of Cryptococcus infection lead to the rhinopharyngitis occurring 4 weeks later and an exanthema resulting finally in a DIC. Following the scoring system for overt DIC, the patient had a score of 7 on admission. As studies could prove a correlation between increasing scores and mortality, the patient’s primary prognosis seemed poor.18,19 In patients with DIC, one has to generally distinguish between cases in where bleeding and cases in where thrombosis predominates. Thus, thrombotic occlusions were the predominant problem in this case. Here, Pernerstorfer et al.20 could show that heparin could inhibit the activation of coagulation in DIC. So our initial treatment seemed to be reasonable. The continuance of continuous infusion of UFH seemed to be the right therapeutic concept as abnormal coagulation parameters could be continuously observed.21 Another option to treat patients with predominantly thrombotic activity is the use of anticoagulant factor concentrates. In the demonstrated case, coagulation factor replacement therapy was not necessary as they showed normal levels of activity. However, it remains uncertain if an underlying
cause of immunodeficiency has led to a temporary altered hemostasis. We plan to perform a variety of additional blood tests when seeing the patient in our Outpatient’s Department to exclude a causal underlying immunodeficiency. We used zymogen protein C supplementation because of reduced activity levels of protein C. It could already be shown that plasma-derived protein C supplementation could reduce mortality in an experimental and clinical setting.22,23 Later observation could prove that patients might profit from protein C supplementation as different from antithrombin concentrate supplementation,24 mortality could significantly be reduced.25,26 As half-life elimination is short and the patient had to undergo several operative treatments, we considered the use of protein C as being reasonable. It could be shown that the amputation rate in critically ill patients with coagulative dysfunction is about 30% and can be reduced using APC to about 10%.27 However, the substitution of zymogen protein C, which has to be activated by the endothelial and platelet thrombinethrombomodulin complexes and the endothelial receptor, could already show his effectiveness.28,29 Theoretically, bleeding complications should occur more seldom using zymogen protein C as autoregulation prevents extraordinary
Vol.
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No.
-, -
2014
Case Report 5
We presented a case of a 61-year-old Caucasian man with a severe case of DIC hypothetical due to contact with pigeon droppings. Clinically, thrombotic occlusion was predominant so that anticoagulation was managed by continuous infusion of UFH and supplementation of APC. The disease resulted in the amputation of both lower legs, both hands, a part of the penis, and the scrotum. As hypoperfusion of the rectum occurred, a descendostoma with rectum extirpation was created. Altogether the patient had to be admitted to the intensive care unit for more than 3 months and could be discharged after 5 months. The case demonstrates severe complication that could be observed in DIC; however, the initial triggering agent remains uncertain.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. REFERENCES
Fig. 3. Representative findings of the CT scan performed emergently after presenting acute abdominal pain. (A) The middle part of the rectum showed radiologic signs of hypoperfusion and local rupture (*). (B) Hydronephrosis grade IIeIII could be found bilaterally. (C) Perihepatic free air could be seen as a sign of a rupture of a hollow organ (**).
high levels of activated protein C. However, this hypothesis needs to be proved in a clinical setting. In addition to our working diagnosis, especially as it could never been evidently proved, there might be other reasons for an arterial late-onset thrombosis also. One might be a constitutional protein C deficiency due to mutations; however, late-onset arterial thrombosis as a clinical symptom is still discussed controversially.30,31 To clarify this, we intend to measure endogenous protein C level and determine the mutation status of the protein C gene when presenting next time in our Outpatient’s Department. Amputations in this case might have been prevented if the diagnosis would have been set earlier. Therefore, recrudescence of priapism might be the first symptom of a DIC. We suggested the patient to take rivaroxaban as anticoagulative medication, however knowing that, in recent literature, there is no guideline for anticoagulative management after DIC up to now.
1. Hewson W. Properties of the Blood. 2nd ed. London (UK): T Cadell, 1772. 2. McKay DG. Trauma and disseminated intravascular coagulation. J Trauma 1969;9:646e60. 3. Kaneko T, Wada H. Diagnostic criteria and laboratory tests for disseminated intravascular coagulation. JCEH 2011;51: 67e76. 4. Hardway R. Syndromes of Disseminated Intravascular Coagulation. Springfield, IL: Thomas CC, 1966. 5. Akca S, Haji-Michael P, de Mendonca A, Suter P, Levi M, Vincent JL. Time course of platelet counts in critically ill patients. Crit Care Med 2002;30:753e6. 6. Carr JM, McKinney M, McDonagh J. Diagnosis of disseminated intravascular coagulation. Role of D-dimer. Am J Clin Pathol 1989;91:280e7. 7. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol 2009;145:24e33. 8. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001;86:1327e30. 9. Toh CH, Hoots WK, ISTH SSCoDICot. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost 2007;5:604e6. 10. Bakhtiari K, Meijers JC, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med 2004;32:2416e21. 11. ten Cate H, Timmerman JJ, Levi M. The pathophysiology of disseminated intravascular coagulation. Thromb Haemost 1999;82:713e7.
6 Case Report
12. Levi M, de Jonge E, van der Poll T, ten Cate H. Disseminated intravascular coagulation. Thromb Haemost 1999;82(2): 695e705. 13. Gando S, Kameue T, Nanzaki S, Nakanishi Y. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome. Thromb Haemost 1996;75:224e8. 14. Chae HS, Park GN, Kim SH, et al. Rapid direct identification of Cryptococcus neoformans from pigeon droppings by nested PCR using CNLAC1 gene. Poult Sci 2012;91:1983e9. 15. Vidotto V, Ito-Kuwa S, Nakamura K, et al. Extracellular enzymatic activities in Cryptococcus neoformans strains isolated from AIDS patients in different countries. Rev Iberoam Micol 2006;23:216e20. 16. Levitz SM. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis 1991;13: 1163e9. 17. Edwards VE, Sutherland JM, Tyrer JH. Cryptococcosis of the central nervous system. Epidemiological, clinical, and therapeutic features. J Neurol Neurosurg Psychiatry 1970;33: 415e25. 18. Wada H, Wakita Y, Nakase T, et al. Outcome of disseminated intravascular coagulation in relation to the score when treatment was begun. Mie DIC Study Group. Thromb Haemost 1995;74:848e52. 19. Angstwurm MW, Dempfle CE, Spannagl M. New disseminated intravascular coagulation score: a useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores. Crit Care Med 2006;34:314e20. quiz 328. 20. Pernerstorfer T, Hollenstein U, Hansen J, et al. Heparin blunts endotoxin-induced coagulation activation. Circulation 1999;100:2485e90. 21. Levi M, Levy M, Williams MD, et al. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med 2007;176:483e90.
Annals of Vascular Surgery
22. Taylor FB Jr, Chang A, Esmon CT, D’Angelo A, ViganoD’Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987;79:918e25. 23. Malato A, Saccullo G, Coco LL, et al. Safety of plasmaderived protein C for treating disseminated intravascular coagulation in adult patients with active cancer. Am J Hematol 2012;87:230e2. 24. Warren BL, Eid A, Singer P, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001;286:1869e78. 25. Dhainaut JF, Yan SB, Joyce DE, et al. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost 2004;2:1924e33. 26. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699e709. 27. White B, Livingstone W, Murphy C, Hodgson A, Rafferty M, Smith OP. An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. Blood 2000;96:3719e24. 28. Baratto F, Michielan F, Meroni M, Dal Palu A, Boscolo A, Ori C. Protein C concentrate to restore physiological values in adult septic patients. Intensive Care Med 2008;34:1707e12. 29. Esmon CT. The protein C pathway. Chest 2003;124(3 Suppl):26Se32S. 30. Maqbool S, Rastogi V, Seth A, Singh S, Kumar V, Mustaqueem A. Protein-C deficiency presenting as pulmonary embolism and myocardial infarction in the same patient. Thromb J 2013;11:19. 31. Tajima K, Yamamoto H, Yamamoto M, Kato Y, Kato T. Adult-onset arterial thrombosis in a pedigree of homozygous and heterozygous protein C deficiency. Thromb Res 2013;131:102e4.
Background: Disseminated intravascular coagulation (DIC) can frequently be observed in patients with severe inflammatory response. It is still correlated with a poor prognosis. Activation of coagulation activity leads to occlusions of small vessels resulting in various organ failure symptoms. In addition, secondary fibrinolysis leads to an increased risk of bleedings and means a therapeutic dilemma. Here, we present a case of a 61-year-old Caucasian man with a severe case of DIC and its clinical complications. Methods: We report the case of a man with a severe case of DIC. Data collection was performed retrospectively. Results: We report the case of a 61-year-old Caucasian man with contact to pigeon droppings in his medical history. This was followed by a rhinopharyngitis, an exanthema, and a recurring priapism. Thrombotic occlusions were predominant on admission, and necrosis of the lower legs, the hands, and the genital resulted in amputation. Hypoperfusion of the rectum and the bladder lead to the creation of a descendostoma and an uretrostoma. Anticoagulation was managed by continuous infusion of unfractionated heparin and activated protein C supplementation. Long-term anticoagulation is managed with rivaroxaban. Conclusions: Cryptococcus soil inhalation may cause severe DIC resulting in extremity amputations; however, effective anticoagulation and activated protein C supplementation might extenuate the progress. As multiple complications might occur, an interdisciplinary cooperation is essential.
In 1772, Hewson1 first described observations that in intense bleeding patients the blood occurring the last clotted earlier than the blood occurring fist. This finding could be repeatedly observed in trauma patients and patients with severe systemic inflammatory response, presumably because of acidosis and high catecholamine levels.2 A widely used synonym for disseminated intravascular coagulation (DIC) is 1 Department of Vascular and Endovascular Surgery, University Hospital D€ usseldorf, D€ ussedorf, Germany. 2 Department of Hemostaseology, University Hospital D€ usseldorf, D€ ussedorf, Germany.
Correspondence to: Markus U. Wagenh€auser, Department of Vascular and Endovascular Surgery, Moorenstrasse 5, 40225 D€ usseldorf, Germany; E-mail: markus.wagenhaeuser@med. uni-duesseldorf.de Ann Vasc Surg 2014; -: 1–6 http://dx.doi.org/10.1016/j.avsg.2014.01.024 Ó 2014 Elsevier Inc. All rights reserved. Manuscript received: September 13, 2013; manuscript accepted: January 14, 2014; published online: ---.
the expression ‘‘death is coming’’3 and demonstrates the severity of the diagnosis. To start the cascade of intravascular clotting, a stimulus needs to be introduced into the organism. The mechanism of introduction and the application rate may be responsible for clinical severity of symptoms.4 There is no laboratory test available to give evidence to the diagnosis of DIC. Low platelet count 30 mm Hg. Inguinal, femoral, and popliteal pulses were palpable bilaterally; however, peripheral pulses were missing. Both feet were acute ischemic, and computed tomography (CT) scans showed a total bilateral and arterial occlusion in the middle of the lower leg with intramuscular hemorrhages and muscular swelling. In addition, mild-hemorrhagic freeabdominal liquid (perihepatic, perisplenic, and retroperitoneal) without signs of an active bleeding could be seen on CT scans. Representative radiologic findings and results of the first blood examinations after admission are shown in Figure 1. Immediate fasciotomy was performed, thrombotic occlusion of the small veins of the lower legs could be observed. Intraoperative angiography showed ruptures of small arteries and bleedings of the anterior tibial artery, explaining the CT scan findings. Skin closure was not possible, so temporarily a negative-pressure wound therapy at both lower legs was initiated. Because of acute
Annals of Vascular Surgery
ischemia of the genitals, the Department of Urology participated in the operation and could find a thrombotic occlusion of the small intracorporal veins; thus, a decompressive punctuation was not possible anymore. The patient was transferred to the intensive care unit. There was no evidence of an endocarditis according to a transthoracic echocardiogram, neither of an immunologicrelated disease according to blood examination results. Thrombotic affinity was predominant, and there was no clinical sign of active bleeding. The coagulative management was arranged in an interdisciplinary consent between the Department of Hemostaseology, the physicians in charge of the intensive care unit, and the Department of Vascular Surgery. As protein C showed a reduced level of activity in the initial blood test results, we substituted a total of 10,000 international units (I.E) Ceprotin (zymogen protein C). The first dose was 70 I.E./kg and the following doses were substituted appropriate to the regularly monitored (every 6 hr) activity level of protein C. In the further course, we started effective anticoagulation by continuous infusion of unfractionated heparin (UFH). The therapeutic range was an aPTT of 50e70 sec. Thus, the mean dose of UFH was about 270 I.E./kg/day. Several attempts to reduce effective anticoagulation (aPPT monitored) and to stop continuous infusion of UFH resulted in increased levels of D-dimers, thus anticoagulation could not be reduced. The patient’s received several red blood cell and plasma transfusions. Moreover, he also received 4 platelet concentrates transfusions. In general, we accepted moderate supressed levels of procoagulative factors as thrombotic affinity was clinically predominant in the absence of any bleeding signs in the further course. The transfusion of purified factors other than zymogen protein C was not necessary. Necrosis of the lower legs proceeded up to the popliteal fossa with progressive muscle necrosis. Necrosis of the hands proceeded up to wrists and necrosis of the genital and anal area were also progressive (Fig. 2). Leg preservation was not possible, and above-knee amputation was performed after complete demarcation. We had to perform amputation of both the hands, the scrotum, and a part of the penis. In the middle of April, the patient showed acute abdominal pain. We conducted an immediate CT scan that showed perihepatic free air and an ischemia of the rectum. Moreover, acute hydronephrosis grade IIe III could be observed. Main findings are shown in Figure 3. Exploratory laparatomy was performed and ended with rectum extirpation and descendostoma creation. The bladder showed regional sign of hypoperfusion; however, there was no indication for resection. Therefore, transurethral splinting of the ureter and protective uretrostoma had to be performed because of consistent hypoperfusion. Hemoglobin decline could be seen twice, so that the patient had to undergo relaparatomy twice. Here, we could find diffusive bleeding, so we performed hematoma removal and attended the accompanying abdominal compartment with an open abdomen and vicryl mesh covering.
Vol.
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No.
-, -
2014
Case Report 3
Fig. 1. Results of the first blood test and representative findings of the first CT scan after admission. Here, results important for the ISTH Diagnostic Scoring System for DIC are presented. (A) Three arteries of the upper part of the lower leg with correct contrast after contrast agent application, demonstrating regular perfusion. (B) No arterial flow can be seen in the middle part of the lower leg after
contrast agent application. A sudden break off of the arterial flow accompanied with muscles swelling could be observed because of arterial occlusion and presented clinically as acute compartment syndrome. (C) Lower pelvis with mild-hemorrhagic free-abdominal liquid (*). No active bleeding could be found.
As the closure of the laparastoma was not possible, we had to await secondary wound healing and could close the laparastoma eventually using a mesh graft from the upper left leg. Screening blood tests, which were done shortly after admission, rejected the suspicion of a rheumatologicrelated disease. Moreover, these blood tests could not prove a subliminal Cryptococcus infection. However, we treated the patient with Amphotericin B at a dose of 1 mg/kg a day for 14 days altogether, knowing that subliminal infections do not always show positive blood test results. Therefore, the effectiveness of the antimycotic therapy remains uncertain. The results of the hematologic blood tests showed the expression of wild-type factor V Leiden and prothrombin. Activated protein C (APC) resistance and heparininduced thrombocytopenia type II could be excluded, and von Willebrand factor showed normal level of activity. The clotting factors II, VII, IX, X, and XIII showed minimally supressed levels of activity, so that the patient did not need coagulation factor replacement therapy. The general condition of the patient improved. A transfer to the ward was possible and performed in the middle of July. Changes of the wound dressings could be performed on the ward. We also supplied a drinking bottle retainer and special bell to increase the patient’s satisfaction and well-being. To achieve an acceptable level of autonomy, alignment of exoprothesis is initiated and an
appointment for rehabilitation has been arranged. Again, the agreement to start rivaroxaban medication as longterm effective anticoagulation has been arranged interdisciplinary.
DISCUSSION We presented a case of severe DIC with many clinical complications resulting in amputation of extremity parts because of vascular occlusions. DIC is a complex and acquired syndrome with activated intravascular coagulation resulting in fibrin formation depositing predominantly in small vessels. As a result, fibrinolysis is activated increasing the risk of bleeding.11,12 Although DIC often occurs in combination with severe sepsis,13 other agents might also be responsible. Our patient’s medical history outlines that he had contact to pigeon droppings 6 weeks before hospital admission. It is known that Cryptococcus can frequently be found in pigeon droppings. It is an encapsulated yeast-like fungus that may cause severe pulmonary and neurologic diseases after contaminated soil inhalation.14,15 Generally, Cryptococcus infections lead to meningitis, pulmonary
4 Case Report
Annals of Vascular Surgery
Fig. 2. Representative pictures of main clinical findings before amputation. (A) Livid discoloration and necrosis up to the middle part of both lower legs. (B) Livid discoloration and necrosis of the left hand marginal above the wrist. The right hand showed equal findings. (C)
Presentation after fasciotomy and application of negative-pressure wound therapy. Both knees showed extensive subcutaneous hemorrhages. (D) Livid discoloration and necrosis of genital. Clinical presentation showed progress and demarcation during hospital stay.
infiltrates, and skin lesions.16,17 Thus, the exanthema might also be a sign of Cryptococcus infection. In our patient, we hypothesized that mild subliminal forms of Cryptococcus infection lead to the rhinopharyngitis occurring 4 weeks later and an exanthema resulting finally in a DIC. Following the scoring system for overt DIC, the patient had a score of 7 on admission. As studies could prove a correlation between increasing scores and mortality, the patient’s primary prognosis seemed poor.18,19 In patients with DIC, one has to generally distinguish between cases in where bleeding and cases in where thrombosis predominates. Thus, thrombotic occlusions were the predominant problem in this case. Here, Pernerstorfer et al.20 could show that heparin could inhibit the activation of coagulation in DIC. So our initial treatment seemed to be reasonable. The continuance of continuous infusion of UFH seemed to be the right therapeutic concept as abnormal coagulation parameters could be continuously observed.21 Another option to treat patients with predominantly thrombotic activity is the use of anticoagulant factor concentrates. In the demonstrated case, coagulation factor replacement therapy was not necessary as they showed normal levels of activity. However, it remains uncertain if an underlying
cause of immunodeficiency has led to a temporary altered hemostasis. We plan to perform a variety of additional blood tests when seeing the patient in our Outpatient’s Department to exclude a causal underlying immunodeficiency. We used zymogen protein C supplementation because of reduced activity levels of protein C. It could already be shown that plasma-derived protein C supplementation could reduce mortality in an experimental and clinical setting.22,23 Later observation could prove that patients might profit from protein C supplementation as different from antithrombin concentrate supplementation,24 mortality could significantly be reduced.25,26 As half-life elimination is short and the patient had to undergo several operative treatments, we considered the use of protein C as being reasonable. It could be shown that the amputation rate in critically ill patients with coagulative dysfunction is about 30% and can be reduced using APC to about 10%.27 However, the substitution of zymogen protein C, which has to be activated by the endothelial and platelet thrombinethrombomodulin complexes and the endothelial receptor, could already show his effectiveness.28,29 Theoretically, bleeding complications should occur more seldom using zymogen protein C as autoregulation prevents extraordinary
Vol.
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No.
-, -
2014
Case Report 5
We presented a case of a 61-year-old Caucasian man with a severe case of DIC hypothetical due to contact with pigeon droppings. Clinically, thrombotic occlusion was predominant so that anticoagulation was managed by continuous infusion of UFH and supplementation of APC. The disease resulted in the amputation of both lower legs, both hands, a part of the penis, and the scrotum. As hypoperfusion of the rectum occurred, a descendostoma with rectum extirpation was created. Altogether the patient had to be admitted to the intensive care unit for more than 3 months and could be discharged after 5 months. The case demonstrates severe complication that could be observed in DIC; however, the initial triggering agent remains uncertain.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. REFERENCES
Fig. 3. Representative findings of the CT scan performed emergently after presenting acute abdominal pain. (A) The middle part of the rectum showed radiologic signs of hypoperfusion and local rupture (*). (B) Hydronephrosis grade IIeIII could be found bilaterally. (C) Perihepatic free air could be seen as a sign of a rupture of a hollow organ (**).
high levels of activated protein C. However, this hypothesis needs to be proved in a clinical setting. In addition to our working diagnosis, especially as it could never been evidently proved, there might be other reasons for an arterial late-onset thrombosis also. One might be a constitutional protein C deficiency due to mutations; however, late-onset arterial thrombosis as a clinical symptom is still discussed controversially.30,31 To clarify this, we intend to measure endogenous protein C level and determine the mutation status of the protein C gene when presenting next time in our Outpatient’s Department. Amputations in this case might have been prevented if the diagnosis would have been set earlier. Therefore, recrudescence of priapism might be the first symptom of a DIC. We suggested the patient to take rivaroxaban as anticoagulative medication, however knowing that, in recent literature, there is no guideline for anticoagulative management after DIC up to now.
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