Background: Thrombotic thrombocytopenic purpura and peripartum cardiomyopathy are potentially lethal complications of pregnancy. We describe a case in which both of these developed in the same patient. The etiologies of both conditions remain uncertain, but they share immune hyperreactivity as a possible cause. Case presentation: A 33-year-old Lankan primigravida gave birth at 38 weeks of gestation by cesarean section when she presented with right-sided abdominal pain and a provisional diagnosis of appendicitis. Her pain persisted postoperatively, and on the second postoperative day, she physicaly collapsed suddenly with abdominal distention. Immediate laparotomy revealed generalized oozing from the peritoneum resulting in hemoperitoneum and intestinal hemorrhage. Her laboratory reports showed microangiopathic hemolytic anemia and thrombocytopenia. She also had elevated liver enzyme, lactate dehydrogenase, and creatinine concentrations. A diagnosis of thrombotic thrombocytopenic purpura was made. After a steady recovery, she was discharged from the hospital on the 16th postoperative day, but 12 hours later, she was readmitted with acute-onset progressively worsening shortness of breath. Echocardiography confirmed peripartum cardiomyopathy. She was treated with a bromocriptine and heart failure regimen. At 6 weeks postpartum, her laboratory test results and cardiac function had improved. Conclusions: A possible autoimmune association might have caused both conditions in our patient. This case report serves as a warning message that pregnant women with one possible condition with autoimmune association could go on to develop other similar conditions. Keywords: Thrombotic thrombocytopenic purpura, Pregnancy, Peripartum cardiomyopathy, Autoimmunity, Immune hyperreactivity Background abdominal pain. Her pain was gradually worsening with Thrombotic thrombocytopenic purpura (TTP) and peri- no change in urinary and bowel habits. Her past partum cardiomyopathy (PPCM) are rare, potentially medical, surgical, family, and psychosocial histories were lethal complications of pregnancy. We report a case in unremarkable. A cesarean delivery was performed with a which both of these conditions developed in the same provisional diagnosis of appendicitis because no other patient. The etiologies of both of these entities are explanation could be found for the pain. A preoperative uncertain, but they share immune hyperreactivity as a platelet count of 130 × 10 /L was noted, but it was not possible cause. investigated further. The delivery was concluded uneventfully with a delivery of a nonasphyxiated baby girl weighing 2.8 kg. The patient’s appendix was noted to Case presentation be normal. Her pain persisted postoperatively, and on A 33-year-old Lankan primigravida was admitted at the second postoperative day, she physicaly collapsed 38 weeks of gestation with episodic right-sided suddenly with abdominal distention. An episode of * Correspondence: email@example.com hematemesis followed shortly afterward. Her University Obstetrics Unit, De Soysa Hospital for Women, Colombo, Sri hemoglobin level was 5 g/dl, and her platelet count was Lanka 60 × 10 /L. Intraperitoneal and intestinal bleeding was Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Senanayake and Patabendige Journal of Medical Case Reports (2018) 12:158 Page 2 of 4 diagnosed, and an emergency laparotomy was of the following occurring within 6 hours of a blood performed. Her conjunctivae were noted to be icteric transfusion: acute respiratory distress, tachycardia, in- (serum total bilirubin level, 11.4 mg/dl). Generalized creased blood pressure, acute or worsening pulmonary oozing from the peritoneum and the uterine incision edema, and evidence of a positive fluid balance . was noted, and altered blood was present in the bowel. Absence of these features in our patient excludes TACO. An upper gastrointestinal endoscopy failed to Lactate dehydrogenase acts as a marker for the extent demonstrate a bleeding point. The patient was given a of hemolysis and response to plasmapheresis . Re- transfusion of 5 U of blood. The results of laboratory ports in the literature show lower rates of relapse after investigations are summarized in Table 1. splenectomy and also with the use of rituximab [6–8]. On the third postoperative day, the patient developed There is a significant risk of relapse in subsequent preg- a focal seizure involving the right arm, but imaging of nancies . Preconception counseling regarding poten- the brain failed to show a focal lesion. A diagnosis of tial risks in subsequent pregnancies is therefore TTP was made, and five cycles of plasmapheresis were important. Because TTP is rare, a high index of suspi- completed. After plasmapheresis, her blood picture sug- cion is required for rapid diagnosis and prompt treat- gested the recovery phase of microangiopathic hemolytic ment. Unexplained occurrence of thrombocytopenia and anemia. Her hematological and biochemical parameters anemia should prompt consideration of the diagnosis returned to normal, and she was discharged on the 16th and immediate evaluation of a peripheral blood smear. postoperative day. At discharge, she had no complaints, Von Willebrand factor (VWF) is a large glycoprotein and her blood pressure was 140/90 mmHg. that circulates in plasma as a series of multimers. It The patient was readmitted 12 hours following dis- plays a major role in primary hemostasis by inducing the charge with a complaint of acute-onset progressively formation of temporary platelet plugs at sites of vascular worsening shortness of breath. She had features of acute injury. Its activity is dependent on the sizes of the multi- left ventricular failure with a heart rate of 120 beats per mers, with ultralarge VWF multimers being biologically minute, blood pressure of 160/100 mmHg, and arterial very potent [9, 10]. Dysfunctional VWF proteolysis oxygen saturation of 90% while on oxygen. She was resulting in the formation of VWF- and platelet- transferred to a coronary care unit, where she received containing thrombi in the microcirculation of organs is aggressive treatment for heart failure. 2D echocardiog- implicated in the pathogenesis of TTP [9, 10]. The raphy showed an ejection fraction of 45%, and a diagno- defective breakdown of VWF is attributed to a severely sis of PPCM was made. Her B-type natriuretic peptide deficient activity of the VWF-cleaving protease level was extremely elevated (31,400 U/L), and her ADAMTS13, a plasma metalloprotease synthesized in troponin I titer was normal, confirming acute heart the liver, kidneys, and endothelium . This protease failure. She was started on bromocriptine, warfarin, and rapidly degrades VWF-platelet strings by proteolytic a heart failure regimen. At 6 weeks postpartum, her cleavage of the VWF subunit, thereby regulating the size ejection fraction had improved to 60%, and she was of the platelet thrombus [9, 10]. Congenital TTP occurs normotensive. as a result of ADAMTS13 mutations, with the debut usually occurring in the first years of life, whereas ac- Discussion quired TTP is associated with autoantibodies against TTP has a classic pentad of clinical features, including ADAMTS13 . Many patients with TTP exhibit posi- fever, thrombocytopenia, hemolytic anemia, neurological tive autoimmune reactions to other antigens, suggesting abnormalities, and renal failure . In our patient, that defective immune regulation may contribute to the hemoperitoneum and hematemesis could be attributed development of TTP . Acquired TTP is considered a to thrombocytopenia of TTP. Early plasmapheresis is specific autoimmune disease characterized by antibodies, the treatment of choice for TTP. Its effectiveness has usually immunoglobulin G, directed against ADAMTS13 been attributed to the removal of ADAMTS13 (a disin- [6, 11]. These ultralarge VWF multimers cause spontan- tegrin and metalloproteinase with a thrombospondin eous platelet aggregation in the microvasculature of the type 1 motif, member 13) autoantibodies and replace- brain, kidney, and heart . These account for the vas- ment of ADAMTS13 activity [2, 3]. Disseminated intra- cular episodes that are typical of TTP. vascular coagulation (DIC) and transfusion-associated PPCM is characterized by left ventricular systolic dys- circulatory overload (TACO) can be other differential function and heart failure. Its pathogenesis is not clear, diagnoses. Even though prothrombin time prolongation but the role of autoimmunity in cardiovascular diseases and downward trend of platelet count were seen in the has become one of the focal points in the field of cardio- first few days in our patient, her D-dimer level was not myopathy and heart failure. The β -adrenergic and M2- high. Therefore, her presentation favors TTP rather than muscarinic receptors belong to the family of cardiac G DIC as the possible diagnosis. TACO includes any four protein-coupled receptors. Circulating autoantibodies Senanayake and Patabendige Journal of Medical Case Reports (2018) 12:158 Page 3 of 4 Table 1 Summary of laboratory results Postoperative Postoperative Postoperative Postoperative Postoperative Postoperative day 2 day 3 day 4 days 5 and 6 day 10 day 14 Hemoglobin (g/dl) 5 9 8.1 8.3 8.9 9.1 Platelet count (per liter) 60 53 40 35 118 190 Reticulocyte count (%) 4.5 – 5.8 –– – Serum creatinine (mg/dl) 1.7 1.8 1.7 1.8 0.6 0.6 Blood urea nitrogen (mg/dl) 106.5 96 112 117 29.5 24 Serum potassium 3.8 3.9 5.3 5.1 3.6 3.7 SGOT (U/L) 79 84 104 111 88 77 SGPT (U/L) 47 77 97 103 80 73 ALP (U/L) 559 – 740 –– – Serum bilirubin (mg/dl) Total 11.4 Direct 7.6 13.6 15 15.7 5.8 4.3 Indirect 3.8 Prothrombin time (S) 16 15 17.1 16 15 16 INR 1.7 1.7 1.5 1.5 1.6 1.7 CRP (mg/dl) 96 –– 105 – Serum total calcium (mmol/L) 1.8 –– – 2.0 – Serum LDH (U/L) –– 1344 1490 310 – Blood picture –– – Microangiopathic Recovery phase of – hemolytic anemia microangiopathic and suggestive of TTP hemolytic anemia D-dimer (mg/dl) –– – 2.76 1.8 Blood culture –– – No growth –– Upper gastrointestinal – No specific bleeding–– – – endoscopy point seen. Brain CT scan – Normal –– – – Brain MRI scan – Normal –– – – Abdominal ultrasound scan –– – – Liver is normal Mild – ascites noted Abbreviations: SGOT Aspartate aminotransferase, SGPT Alanine aminotransferase, ALP Alkaline phosphatase, INR International normalized ratio, CRP C-reactive pro- tein, LDH Lactate dehydrogenase, CT Computed tomography, MRI Magnetic resonance imaging, TTP Thrombotic thrombocytopenic purpura against the second extracellular loop of β -adrenergic AABs were positively correlated with left ventricular di- receptors and M2-muscarinic receptors have been mensions and negatively correlated with the cardiac detected in a number of cardiovascular diseases charac- function of patients with PPCM . The autoantibodies terized by heart failure, including idiopathic dilated car- of cardiovascular receptors were independent risk diomyopathy and chronic Chagas heart disease [12, 13]. factors for the onset of PPCM . After 12 months of Patients with PPCM have been confirmed to be positive treatment for PPCM, the frequency and geometric mean for autoantibodies against β -adrenergic receptors (β R- titers of both β R-AABs and M R-AABs decreased sig- 1 1 1 2 AABs) and autoantibodies against M2-muscarinic recep- nificantly . These have led to a proposal that auto- tors (M R-AABs). High titers of autoantibodies against antibodies against cardiovascular receptors may be selected cardiac tissue proteins have been found in the involved in the pathogenesis of PPCM . majority of women with PPCM . An autoimmune Effective management of PPCM reduces mortality and mechanism is believed to participate in the pathogenesis increases the number of women who fully recover their of PPCM [15, 16]. left ventricular function . Outcomes for subsequent A recent study has demonstrated the presence of β R- pregnancies are better in women who have fully recov- AABs and M R-AABs in patients with PPCM . ered cardiac function after PPCM . However, recur- Positivity rates and serum titers of β R-AABs and M R- rence of cardiac failure is common in subsequent 1 2 Senanayake and Patabendige Journal of Medical Case Reports (2018) 12:158 Page 4 of 4 pregnancies . We used bromocriptine, which has and implementation of universal leukoreduction of blood transfusions. Transfusion. 2010;50:2738–44. been shown to be effective in PPCM, to treat our patient 5. James N, George MD. Thrombotic thrombocytopenic purpura. N Engl J . There is one other case report in the literature Med. 2006;354:1927–35. describing cardiomyopathy occurring in pregnancy in 6. Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other association with TTP. This was reversed rapidly with thrombotic microangiopathies. Br J Haematol. 2012;158:323–35. combined plasma exchange and infusion . 7. Crowther MA, Heddle N, Hayward CPM, et al. Splenectomy done during hematologic remission to prevent relapse in patients with thrombotic thrombocytopenic purpura. Ann Intern Med. 1996;125:294–6. Conclusions 8. Ono T, Mimuro J, Madoiwa S, et al. Severe secondary deficiency of von Our patient had two potentially lethal conditions of un- Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis- induced disseminated intravascular coagulation: its correlation with known etiology. Interestingly, the most plausible explan- development of renal failure. Blood. 2006;107:528–34. ation for both conditions is an autoimmune mechanism. 9. Manea M, Karpman D. Molecular basis of ADAMTS13 dysfunction in thrombotic thrombocytopenic purpura. Pediatr Nephrol. 2009;24(3):447–58. Abbreviations 10. Feys HB, Liu F, Dong N, Pareyn I, Vauterin S, et al. ADAMTS-13 plasma level ADAMTS13: A disintegrin and metalloproteinase with a thrombospondin type 1 determination uncovers antigen absence in acquired thrombotic motif, member 13); β R-AABs: Anti-β -adrenergic receptor autoantibodies; 1 1 thrombocytopenic purpura and ethnic differences. J Thromb Haemost. DIC: Disseminated intravascular coagulation; M R-AABs: Anti-M2-muscarinic 2006;4(5):955–62. receptor autoantibodies; PPCM: Peripartum cardiomyopathy; TACO: Transfusion- 11. Coppo P, Bengoufa D, Veyradier A, et al. Severe ADAMTS13 deficiency in associated circulatory overload; TTP: Thrombotic thrombocytopenic purpura; adult idiopathic thrombotic microangiopathies defines a subset of patients VWF: von Willebrand factor characterized by various autoimmune manifestations, lower platelet count, and mild renal involvement. Medicine (Baltimore). 2004;83:233–44. Acknowledgements 12. Fu LX, Magnusson Y, Bergh CH, Liljeqvist JA, Waagstein F, et al. Localization We thank to all the staff who helped in managing our patient for a good outcome. of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy. J Clin Invest. Availability of data and materials 1993;91:1964–8. The datasets created during and/or analyzed during this case are available from 13. Sterin-Borda L, Gorelik G, Borda E. Chagasic IgG bingding with cardiac the corresponding author on reasonable request. muscarinic cholinergic receptors modifies cholinergic-mediated cellular transmembrane signals. Clin Immunol Immunopathol. 1991;61:389–97. 14. Selle T, Renger I, Labidi S, Bultmann I, Hilfiker-Kleiner D. Reviewing Authors’ contributions peripartum cardiomyopathy: current state of knowledge. Future Cardiol. Both authors contributed equally to this work. Both authors read and approved 2009;5:175–89. the final manuscript. 15. Liu J, Wang Y, Chen M, Zhao W, Wang X, Wang H, Zhang Z, Zhang J, Xu L, Chen J, Yang X, Zhang L. The correlation between peripartum Ethics approval and consent to participate cardiomyopathy and autoantibodies against cardiovascular receptors. PLoS Not applicable. One. 2014;9(1):e86770. 16. Ansari AA, Fett JD, Carraway RE, Mayne AE, Onlamoon N, Sundstrom JB. Consent for publication Autoimmune mechanisms as the basis for human peripartum Written informed consent was obtained from the patient for publication of cardiomyopathy. Clin Rev Allergy Immunol. 2002;23(3):301–24. this case report and any accompanying images. A copy of the written 17. Sliwa K, Hilfiker-Kleiner D, Petrie MC, Mebazaa A. Current state of knowledge consent is available for review by the Editor-in-Chief of this journal. on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of Competing interests the European Society of Cardiology Working Group on peripartum The authors declare that they have no competing interests. cardiomyopathy. Eur J Heart Fail. 2010;12(8):767–78. 18. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet. 2006; 368(9536):687–93. Publisher’sNote 19. Murali S, Baldisseri MR. Peripartum cardiomyopathy. Crit Care Med. 2005; Springer Nature remains neutral with regard to jurisdictional claims in 33(10 Suppl):S340–6. published maps and institutional affiliations. 20. Cosmai EM, Puzis L, Tsai HM, Lian EC. Thrombocytopenic purpura and cardiomyopathy in pregnancy reversed by combined plasma exchange and Author details infusion. Eur J Haematol. 2002;68(4):239–42. 1 2 Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. University Obstetrics Unit, De Soysa Hospital for Women, Colombo, Sri Lanka. Received: 31 October 2017 Accepted: 27 April 2018 References 1. Gaddam S, Pablani L, Chainani V, Kavuda RR. Complete recovery of ischemic cardiomyopathy from thrombotic thrombocytopenic purpura. Clin Med Insights Cardiol. 2011;5:29–33. 2. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med. 1991;325:393–7. 3. Sadler JE, Moake JL, Miyata T, George JN. Recent advances in thrombotic thrombocytopenic purpura. In: Hematology Am Soc Hematol Educ Program; 2004. p. 407–23. 4. Blumberg N, Heal JM, Gettings KF, Phipps RP, Masel D, Refaai MA, et al.An association between decreased cardiopulmonary complications transfusion- related acute lung injury and transfusion-associated circulatory overload
Journal of Medical Case Reports – Springer Journals
Published: Jun 6, 2018
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