Background: Incidences of immune thrombocytopenic purpura occur in 1 in every 1000–10,000 pregnancies accounting for 3% of all thrombocytopenic pregnancies. A pre-existing immune thrombocytopenic purpura is known to be a risk factor for developing thrombocytopenia during pregnancy. We present here the treatment regime and management of a patient with known immune thrombocytopenic purpura who developed postpartum thrombotic thrombocytopenia with atypical response to traditional therapy. Pregnant women are more vulnerable to immune thrombocytopenic purpura or thrombotic thrombocytopenia. Pregnancy or postpartum thrombotic thrombocytopenia accounts for 10–25% of all thrombotic thrombocytopenia. Case presentation: This case report deals with the treatment regime and management of a patient with known immune thrombocytopenic purpura who developed postpartum thrombotic thrombocytopenia. A 30-year-old Middle Eastern woman, with a prior diagnosis of chronic immune thrombocytopenic purpura had remained off- the-treatment for many years. After primary unexplained infertility for 8 years, for which she underwent six failed trials of in vitro fertilization, she delivered a healthy baby through caesarean section. Two days post-surgery, she had persistent thrombocytopenia, ecchymoses, bruises, and hemolysis. Her blood film revealed leukoerythroblastic anemia. Her blood tests also revealed a very low level of haptoglobin, and low level of ADAMTS13. A diagnosis of thrombotic thrombocytopenia was suspected. Plasma exchange therapy was started with partial response. We showed that rituximab in conjunction with mycophenolate mofetil following plasma exchange therapy was effective in controlling the low platelet count in our patient. Conclusions: Rituximab in conjunction with mycophenolate mofetil following plasma exchange therapy was effective in controlling the low platelet count in our patient. Only two doses of rituximab were sufficient to normalize our patient. We present here a case of safe and effective use of rituximab in pregnancy-induced thrombotic thrombocytopenia. Keywords: ITP, TTP, Postpartum, Plasmapheresis * Correspondence: Husban48@yahoo.com Faculty of Medicine, University of Jordan and Jordan University Hospital, PO Box 2194, Amman 11941, Jordan © 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. Al-Husban and Al-Kuran Journal of Medical Case Reports (2018) 12:147 Page 2 of 7 Background dose was tapered gradually down to 15 mg at 34 weeks of The occurrence of immune thrombocytopenic purpura gestation. At 35 weeks, her whole blood platelet count was (ITP) or thrombotic thrombocytopenia (TTP) is greatly 45 × 10 /L, her blood hemoglobin (Hb) level was 125 g/L increased during pregnancy. Incidences of ITP occur in with an A-positive blood group, and she was asymptom- 1inevery 1000–10,000 pregnancies accounting for 3% atic with normal blood pressure (BP) and urine analysis. of all thrombocytopenic pregnancies . Pregnancy or By 36 weeks of gestation, she presented with ruptured postpartum-related TTP accounts for 10–25% of all membranes, with no uterine contractions. Her BP, oral TTP. A pre-existing ITP is known to be a risk factor temperature, and pulse rate were 120/70 mmHg, 37.1 for developing thrombocytopenia during pregnancy . degrees Celsius and 90 beats/minute, respectively. Her We present here the treatment regime and manage- general examination was unremarkable. An obstetric ment of a patient with known ITP who developed post- examination revealed a cephalic presentation and a fun- partum TTP with atypical response to traditional dal height that was corresponding to a 36-week preg- therapy. The unusualness of this case was the onset of nancy. There were no skin lesions. Her neurological presentation (postpartum) and the bruises and ecchym- examination was normal with no focal neurological defi- osis which were the main clinical features. These fea- cits. A cardiotocography (CTG) was performed and was tures are not known to be associated with ITP and normal. Her Hb, white blood cell (WBC) count, and 9 9 medical staff has to be very vigilant and careful with platelet count were 130 g/L, 12 × 10 /L, and 33 × 10 /L, these cases. respectively. Her liver function tests were normal: lactate dehydrogenase (LDH) 3.0 ukat/L and bilirubin total 8 Case presentation umol/L. She insisted on caesarean section delivery A 30-year-old married Middle Eastern woman, a despite thorough counselling regarding the mode of housewife living in a big city in Jordan, with a prior delivery. She was given intravenously 500 mg of diagnosis of chronic ITP remained off-the-treatment methylprednisolone and intramuscularly 1500 IU of for many years. She was not known to have any other anti-D immunoglobulin in an attempt to quickly raise medical illness. There was no family history of ITP or her platelet count. Six hours later, an uncomplicated cae- TTP. She had never smoked tobacco, drunk alcohol, sarean section was performed under spinal anesthesia or used illicit drugs. She was investigated for other (she refused to have a general anesthetic and requested a causes of thrombocytopenia including systemic lupus spinal anesthesia despite counselling regarding the risk erythematosus (SLE)-antiphospholipid antibody syn- of hematoma because of her low platelet count). A drome (APS) but, unfortunately, the laboratory- healthy baby was delivered weighing 2.3 kg with normal specific results were not available, however, our pa- platelet count. No instance of bleeding was noted during tient stated that they were negative. Initially she was pre- the surgery. The operative blood loss was estimated to scribed a low dose of orally administered prednisolone but be around 1000 ml. Recovery after surgery was smooth. this was discontinued years ago. She remained asymptom- She was given low molecular weight heparin (LMWH) atic with approximate whole blood platelet counts of 50 × (40 mg of enoxaparin sodium), subcutaneously 12 hours 10 /L. She had primary unexplained infertility for 8 years after operation. for which she underwent six failed trials of in vitro Postoperatively on day 1, she was doing well with stable fertilization (IVF). She conceived spontaneously and vital signs and no abnormal vaginal bleeding. No incidence remained asymptomatic with whole blood platelet counts of bruises or ecchymosis around the wound or anywhere >50 × 10 /L. At 26 weeks of gestation, she was diagnosed else was noted. Her platelet count, WBC, and Hb were 9 9 as having glucose intolerance and started on metformin 46 × 10 /L, 18.35 × 10 /L, and 96 g/L, respectively. She 850 mg twice daily. At 30 weeks of gestation, her whole was started on 30 mg of orally administered prednisolone. blood platelet count was 30 × 10 /L and she was still On the second postoperative day, ecchymosis started to asymptomatic. She was started on 15 mg orally appear around the wound. Her BP and urine analysis were administered prednisolone. One week later, her whole normal. She had a platelet count of 52 × 10 /L. Although blood platelet count dropped to 28 × 10 /L, her she was reassured about the safety of breast feeding, she prednisolone dose was increased to 30 mg daily. She was was not happy to breast feed and she had no breast pain screened for lupus anticoagulant, anticardiolipin antibody or engorgement. In the afternoon, the bruises and (ACA), and anti-beta-2 glycoprotein 1 (BTIIGLYI) anti- ecchymosis spread across her lower abdomen and down body and the results were normal: partial thromboplastin to her upper thighs. A hematologist was consulted who time (PTT) 27 seconds, ACA-immunoglobulin G (IgG) < 14 advised observation only. GPL, ACA-IgM < 12 MPL, BTIIGLYI-IgM 16 U/mL, and On the third postoperative day, the ecchymosis ex- BTIIGLYI-IgG 17 U/mL. Two weeks later, her whole panded bilaterally over her suprapubic area, vulval area, blood platelet count was 56 × 10 /L. Her prednisolone flanks, and thighs. She complained of occipital headache Al-Husban and Al-Kuran Journal of Medical Case Reports (2018) 12:147 Page 3 of 7 which was relieved by simple analgesia, there were no 56 × 10 /L; total bilirubin, direct bilirubin, ALT, AST, other neurological symptoms or signs. Her BP was nor- and urine analysis were normal. TTP was suspected; mal. An abdominal ultrasound (U/S) scan revealed an hence, ADAMTS13 test was requested. The result empty uterus with no free fluid in her abdomen or pelvis indicated 11%. The next day, her bruises and ecchymosis and no evidence of presence of hematoma. Her whole were extensive and spreading. She was doing well with blood Hb was 88 g/L, WBC was 12.89 × 10 /L, and no neurological symptoms and stable vital signs. Her platelet count was 50 × 10 /L. We suspected a hemolytic urine was normal. Blood film revealed plenty of process so a liver function test, haptoglobin, and blood schistocytes. TTP was strongly suspected; she was given film were requested. These revealed total serum 5 units of fresh frozen plasma (FFP). Eight hours after bilirubin 17.07 umol/L, direct serum bilirubin 5.97 the FFP infusion, her platelet count was 76 × 10 /L. umol/L, total serum protein 55.6 g/L, serum albumin 34. Bruises decreased the day after FFP infusion. Plasma- 4 g/L, serum alanine aminotransferase (ALT) 0.47 ukat/ pheresis (a left femoral dialysis line was inserted under L, serum aspartate aminotransferase (AST) 0.80 ukat/L, aseptic technique) was started. The first session was serum gamma glutamyltransferase (GGT) 0.55 ukat/L, done with 10 units of FFP and 4 units of cryoprecipitate. and serum LDH 21.1 ukat/L. Her serum haptoglobin Investigations showed normal Hb, WBC, platelet count, level was low, 100 mg/L, with negative direct and liver function tests, and urine. On the successive day, indirect Coombs tests. Her urine was normal. Blood film bruises and ecchymosis decreased. LDH was 15.8 ukat/L showed normocytic red cell anemia, polychromasia, few with normal creatinine, calcium, phosphorous, magne- schistocytes, one to two nucleated red blood cells (RBCs)/ sium, total bilirubin, direct bilirubin, ALT, AST, GGT, 100 WBCs, neutrophilic leukocytosis, occasionally left PT, PTT, and fibrinogen level. A urine examination shifted neutrophils, and thrombocytopenia with large showed + 1 proteinuria. A second session of plasmapher- forms. Three ampoules of iron sucrose complex were esis was done. On the next day, her platelet count was given intravenously over 3 hours and she was started on 60 × 10 /L and Hb was 99 g/L with normal liver and orally administered iron. kidney functions. Her LDH was 13.7 ukat/L, with normal Four days after surgery, she was doing well apart from PT, PTT, and fibrinogen level. Blood film showed recurrent attacks of headache. Her BP was normal and leukoerythroblastic anemia, anisocytosis, polychromasia, she had no focal neurological signs. Her serum vitamin schistocytes, and spherocytes. A third session of B12 level, serum iron, serum folate level, serum ferritin plasmapheresis was done. Following FFP infusion and level, plasma prothrombin time (PT), whole blood PTT, plasmapheresis, ADAMTS13 level was > 19%. and plasma fibrinogen were normal. Her newborn’splate- On the 12th postoperative day, a fourth session of let count was normal. Total as well as direct bilirubin and plasmapheresis was done. Her LDH was 10.8 ukat/L LDH were elevated: 26.4 umol/L, 7.2 umol/L, and 26.7 with normal kidney and liver functions. Her platelet ukat/L, respectively. Five days after surgery, there were se- count was 54 × 10 /L. vere and extensive bruises as well as ecchymosis. No ab- After the fifth session of plasmapheresis, LDH was 8. normal vaginal bleeding or epistaxis was seen. Orally 56 ukat/L. PT, PTT, and fibrinogen level were normal. administered mycophenolate mofetil 360 mg was started Ecchymosis decreased substantially. Our patient was twice daily in addition to the daily 30 mg orally adminis- asking for discharge. tered prednisolone she was already taking. The next day, her platelet count was 52 × 10 /L; LDH On the sixth postoperative day, ecchymosis was seen all was 13.4 ukat/L with normal liver and kidney functions. A over her abdomen, flanks, thighs, legs, and low back area. sixth session of plasmapheresis was carried out. A urine Her Hb was 83 g/L, WBC 16.6 × 10 /L, platelet count examination showed + 1 proteinuria. During all these 50 × 10 /L, and LDH 28.7 ukat/L, and she had normal days, our patient was on 1 mg/kg orally administered total bilirubin, direct bilirubin, random serum glucose, prednisolone per day and 360 mg orally administered sodium, potassium, urea, and creatinine. Urine analysis mycophenolate twice daily. Ecchymosis decreased further showed + 1 proteinuria, no sugar, one to two WBC/high on the following day. She was given intravenously power field (HPF), and 2–4 RBC/HPF. Indirect and direct rituximab 500 mg in 5 hours. Her LDH level was 11.0 Coombs tests were negative. Two ampoules of iron ukat/L, platelet count was 100 × 10 /L, Hb 111 g/L, and sucrose were administered intravenously in 2 hours. WBC 7.92 × 10 /L. She was discharged with a prescription Prednisolone dose was increased to 1 mg/kg daily. for orally administered prednisolone 1 mg/kg daily and Bruises and ecchymosis increased 1-week post-surgery. 360 mg of orally administered mycophenolate twice daily. Blood film revealed leukoerythroblastic anemia, anisocy- One week later, she was given the second dose of tosis, nine nucleated red cells/100 WBC, 8% left shifted rituximab as an out-patient. She continued to do well neutrophils, and thrombocytopenia with few large forms. with no bleeding tendency and a platelet count swinging 9 9 Her LDH level was 28.4 ukat/L. Her platelet count was between 50 × 10 /L and 60 × 10 /L. Al-Husban and Al-Kuran Journal of Medical Case Reports (2018) 12:147 Page 4 of 7 At 4 weeks after surgery, her Hb, WBC, and platelet is diagnosed by exclusion of other diseases due to lack of 9 9 count were 128 g/L, 13.7 × 10 /L, and 130 × 10 /L, concrete biomarkers . In this case report we present a respectively. Her liver and kidney function tests were case in which a chronic history of ITP which remained normal. Two weeks later, her platelet count was 80 × asymptomatic for years was precipitated as TTP after 10 /L. After a further 2 weeks, she continued to receive delivery. Further, we discuss the difficulties encountered the same mycophenolate dose but started to decrease in the diagnosis of TTP in the postpartum woman as her prednisolone dose until it was completely stopped well as the management of the patient. 3 weeks later. A corticosteroid, such as prednisolone, is the first line Ten weeks after surgery, she became asymptomatic of therapy for ITP . It increases the platelet count in with a platelet count of 92 × 10 /L. She was receiving 2–4 weeks. However, in our case, the intake of a high only mycophenolate mofetil at a dose of 360 mg twice dose of orally administered prednisolone initially with daily. She stopped mycophenolate mofetil and remained doses tapering in the later part making a total of 4 weeks completely asymptomatic. Six months after delivery, she was ineffective in increasing our patient’s platelet count. was asymptomatic with a platelet count of 85 × 10 /L. Intravenous administration of anti-D with or without One year after her delivery, she was doing well, steroids increases the platelet count rapidly in patients asymptomatic, and her platelet count was 79 × 10 /L. with ITP . It is suitable for Rhesus antigen D (RhD) Table 1 refers to results of patient’s blood tests in a positive patients who are not splenectomized as in our chronological order. case. Baseline Hb has a significant impact on platelet re- sponse to anti-D in adults . Anti-D is also known to Discussion cause hemolysis and this is more pronounced 1 day after This was a case of pregnancy-triggered TTP in a patient its administration ; this was not the scenario in our with chronic ITP. Moreover, she underwent a caesarean case. Similarly, methylprednisolone is more effective section under a spinal anesthetic with severe than prednisolone in increasing the platelets count in thrombocytopenia and did not experience hemorrhagic thrombocytopenia . Administration of methylprednis- complications. It unusually presented in the immediate olone and anti-D a few hours before delivery by caesar- postpartum period and was not a typical TTP; it did not ean section in our patient was effective in preventing respond to the traditional management pathways. excessive blood loss. TTP is a rare life-threatening disease which requires However, except for thrombocytopenia and microan- rapid intervention. Pregnancy is a known trigger for giopathic hemolytic anemia, which occur frequently thrombocytopenia. A previous history of ITP aggravates (50–75%), other symptoms of TTP are either not present thrombocytopenia in pregnancy . However, to date it or vaguely observed. Therefore, thrombocytopenia, Table 1 Shows results of patient’s blood tests in a chronological order Days 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Hb (g/L) 96 88 83 99 111 Platelets (×10 /L) 46 52 50 50 49 60 54 52 100 WBC (×10 /L) 18.35 12.89 16.6 7.9 Total bilirubin (umol/L) 17.07 26.4 Direct bilirubin (umol/L) 5.97 7.2 Total protein (g/L) 55.6 Albumin (g/L) 34.4 ALT (ukat/L) 0.47 AST (ukat/L) 0.80 GGT (ukat/L) 0.55 LDH (ukat/L) 21.1 26.7 28.7 28.4 15.8 13.7 10.8 13.4 11.0 Haptoglobin (mg/L) 100 Direct Coombs Negative Negative Indirect Coombs Negative Negative Serum glucose (mmol/L) 4.1 Serum creatinine (umol/L) 90 ALT alanine aminotransferase, AST aspartate aminotransferase, GGT gamma glutamyltransferase, Hb hemoglobin, LDH lactate dehydrogenase, WBC white blood cells Al-Husban and Al-Kuran Journal of Medical Case Reports (2018) 12:147 Page 5 of 7 microangiopathic hemolytic anemia, and absence of al- Identifying the presence of hemolytic anemia and its ternative etiology are sufficient to diagnose TTP [6, 7]. underlying cause is of prime importance in diagnosing This allows physicians to diagnose TTP rapidly, which can TTP. The presence of schistocytes, the fragmented RBCs be of lifesaving importance. Incidences of TTP are also in- injured by damaged endothelium, in blood film investi- creasingly associated with pregnancy . TTP can com- gation is one of the strong indicators of hemolytic mence at any time in pregnancy. In a study, out of 13 anemia [12, 13]. However, identifying it microscopically pregnancies complicated by thrombotic microangiopathies lacks standardization and is dependent on the evaluator. (TMA), three patients had onset before mid-pregnancy, A threshold of 0.2–0.5% schistocytes is necessary before eight had onset during peripartum, and two several weeks suspecting TTP. In our case the few schistocytes were postpartum . In our case, thrombocytopenia was de- observed on third day post-surgery which increased tected during the third trimester while TTP was symp- drastically in 5 days. Although hemolysis (fragmented tomatologically evident (by ecchymosis) at second day RBCs) was indicative in our case the decrease in Hb in our after delivering the baby by caesarean section. In our case, patient was not drastic (Hb changed from 96 to 83 g/L in 1 even though thrombocytopenia was present during the week). However, schistocytes are not specific for TTP, but third trimester of gestation, the hemolytic anemia precipi- arealsoseeninhealthypersons as wellas inpatients with tated on second postoperative day. With the exception of preeclampsia, eclampsia, chronic renal failure, solid organ the recurrent attacks of headache and proteinuria, her or bone marrow transplantation, diabetic microangiopathy, renal function and nervous system were normal without and SLE, as well as in patients with a prosthetic heart valve any episodes of fever. Because TTP typically does not have [14, 15]. Severe bleeding is a common cause for the appear- a bleeding tendency, the possibility of a migrating sub- ance of nucleated RBCs in peripheral blood smears in cutaneous hematoma after the caesarean section with addition to reticulocytosis, but our patient did not have any spinal anesthesia, which could have been facilitated by the bleeding episode. Therefore, the laboratory findings which single dose of LMWH, was excluded by a normal U/S appeared important in the diagnosis of TTP were high scan of her abdominal wall, abdominal cavity, and pelvis. LDH to AST ratio since an increased LDH-to-AST ratio is Severe deficiency of ADAMTS13 is the underlying cause known to indicate TTP [16, 17]. High LDH levels along for developing TTP . In acquired TTP this is mediated with elevated creatine kinase are observed after surgery by auto-antibodies against ADAMTS13. An ADAMTS13 including caesarean section and are not always conclusive value of < 10% is indicative of TTP. However, ADAMTS13 for hemolysis. Usually a negative Coombs test shows that levels can also be lowered (but > 10%) in pregnancy, post- the reason for hemolysis is TTP while a positive Coombs partum, and other non-TTP diseases such as hemolytic test suggests an immune-mediated reason for hemolysis uremic syndrome, hematopoietic stem cell and solid organ . Other causes of secondary TTP like DIC or APS are transplantation, liver disease, disseminated intravascular co- unlikely in our case because our patient was screened nega- agulation (DIC), sepsis, certain medications , preeclamp- tive for APS and she had no excessive bleeding or blood sia, eclampsia, and hemolysis, elevated liver enzymes, and transfusion to indicate a possible DIC. low platelet count (HELLP) [10, 11]. Moreover, interfer- Early diagnosis of TTP and management of its symp- ences in the assay measuring ADAMTS13 can occur from toms acutely with advanced techniques such as plasma a high concentration of von Willebrand factor (vWF), exchange therapy (PEX) is necessary as delay in initiat- hyperlipidemia, hemolysis with plasma free Hb > 2 g/L, and ing PEX is known to cause adverse outcomes [3, 19]. hyperbilirubinemia, and cleavage by other proteases can Normally, two to three sessions of PEX are sufficient to even complicate identification of TTP . Besides, recent stabilize the platelet count , however, in our case, our plasma exchange or transfusion may falsely normalize patient achieved only symptomatological (ecchymosis ADAMTS13 levels, thus potentially masking the diagnosis decreased) relief and her LDH began to decrease after of TTP. Therefore, TTP remains a challenge in clinical administration of PEX. Her platelet count failed to reach diagnosis. In our patient, ADAMTS13 activity was 11%. normal levels while her Hb level was also within 99 g/L Although undetectable levels of the enzyme activity are range. Administration of immunosuppressant mycophe- diagnostic of inherited or acquired TTP, not all patients nolate mofetil as well as corticosteroid prednisolone diagnosed as having TTP have severe protease deficiency, along with PEX was ineffective in increasing her platelet and it is therefore not recommended as an initial test for count and Hb level. In a few cases of ITP and TTP, my- diagnosis. Therefore, based only on the ADAMTS13 cophenolate mofetil has been shown to increase the level, a concrete diagnosis of TTP is difficult. The rise platelet count as well as Hb [20–22]. in the level of ADAMTS13 activity with plasma infu- Rituximab is known to be a safe and effective treat- sion and plasmapheresis was in support of a diagnosis ment for newly diagnosed TTP and ITP; it decreases the of TTP. Moreover, support from other laboratory diag- number of PEX required for achieving remission and noses is very necessary. lowers the risk for recurrence by approximately 80%. In Al-Husban and Al-Kuran Journal of Medical Case Reports (2018) 12:147 Page 6 of 7 addition, unresponsiveness to steroids in chronic ITP is PEX: Plasma exchange therapy; PT: Prothrombin time; PTT: Partial thromboplastin time; RBC: Red blood cell; SLE: Systemic lupus erythematosus; relatively common and fast responses to rituximab can TMA: Thrombotic microangiopathies; TTP: Thrombotic thrombocytopenia; U/ be seen. Diagnostic consideration, therefore, cannot de- S: Ultrasound; vWF: Von Willebrand factor; WBC: White blood cell pend on the response to these therapies since they are Availability of data and materials both used effectively in both ITP and TTP [23, 24]. The data presented in this case report are the original patient’s data. However, a review of 231 pregnancies indicated that ri- Therefore, the authors will not share it in an additional file. tuximab is able to cross the placental barrier and induce neonatal hematological abnormalities or malformations Authors’ contributions NA-H was the patient’s consultant and the main writer. OA-K contributed to . Contrarily, in a study by Scully et al., administra- the literature search and writing up of the paper. Both authors read and tion of rituximab in a woman with pregnancy-related approved the final manuscript. TTP was found to be safe and effective . Application Ethics approval and consent to participate of rituximab along with PEX or shortly after PEX re- Approval from the Department of Obstetrics and Gynaecology at Jordan quires a greater number of applications of the medica- University Hospital was obtained for this case publication. tion to be effective because rituximab is removed from Consent for publication the circulation by the PEX . Intravenous supply of ri- Written informed consent was obtained from the patient for publication of tuximab, following PEX, not only rapidly increased the this case report. A copy of the written consent is available for review by the platelet count and Hb in our patient but also controlled Editor-in-Chief of this journal. her WBC count, which was slightly elevated, and nor- Competing interests malized her LDH level. Our treatment regime of first The authors declare that they have no competing interests. performing multiple PEX to remove the inhibitors of ADAMTS13 and then applying rituximab was more ef- Publisher’sNote fective and rapid. After a second dose of rituximab our Springer Nature remains neutral with regard to jurisdictional claims in patient was completely normal with normal platelet published maps and institutional affiliations. counts. 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Journal of Medical Case Reports – Springer Journals
Published: Jun 1, 2018
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