Clinical study of 9 patients with acquired thrombotic thrombocytopenic purpura

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1 Journal of Clinical and Experimental Medicine VOL.1,ISS.3,DEC 2017,1-5 ONLINE ISSN: PRINT ISSN: DOI: /jocem Abstract: Clinical study of 9 patients with acquired thrombotic thrombocytopenic purpura Objective: To analyze the clinical features, treatment strategies and outcomes of patients with acquired thrombocytopenic purpura (TTP). Methods: The clinical data of 9 patients with acquired TTP were retrospectively analyzed. Using SPSS 13.0 software for data analysis. Results: There were 4 males and 5 females in 9 patients, with a median age of 43 (24-72) years. Five patients (55.56%) showed typical pentadia syndrome. Thrombocytopenia (100%), microangiopathy Anemia (100%), fever (88.89%) is more common, while the nervous system symptoms (77.78%) and kidney damage (55.56%) is relatively rare. Two patients were tested for plasma von Willebrand factor (ADAMTS13) activity, with activities of 2.4% and 4.4%, respectively. Four patients (44.44%) were treated effectively, and the effective rate of plasma exchange and plasma infusion was 55.56%. Five patients died without recurrence. The average age of onset of death was higher than that of the effective patients (52.2 ± VS ± 11.44), but the difference was not statistically significant (P = 0.081). Conclusion: Concurrent clinical fever, hemolysis and bleeding tendency need to consider the possibility of TTP. Detection of plasma ADAMTS13 activity contributes to the clinical diagnosis of TTP. Early diagnosis and timely application of plasma therapy can help control the disease. The prognosis of elderly patients is relatively poor. Hong Qu Pan Yu Central Hospital, GuangDong, China keywords: Purpura, thrombotic thrombocytopenia; von Willebrand factor lyase; clinical features; treatment Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized primarily by microvascular hemolytic anemia (MAHA), reduced platelet aggregation depletion, and organ damage caused by thrombosis (eg, the kidney, central nervous system, etc.). TTP has low incidence, high mortality and the presence of multiple system symptoms and misdiagnosis, missed diagnosis, leading to miss the best timing of treatment. Clinically, according to the genetic background it is divided into hereditary TTP and acquired TTP. The latter is divided into idiopathic and secondary according to whether there are obvious incentives. Most cases are idiopathic, no special cause can be found, the disease is easy to recurrent; secondary has a specific reason, having an increasing incidence in recent years,. We retrospectively analyzed the clinical features, treatment strategies and outcomes of 9 patients with acquired TTP, and the report is as follows. Cases and methods 1.General Information: 9 patients with acquired TTP were admitted to Panyu Central Hospital of Guangzhou from April 2010 to May TTP diagnosis of all patients was in line with the standard [1]. There were 4 males and 5 females, with a median age of 43 (24-72) years (Table 1). 2.Research Methods: All cases are in line with TTP diagnostic criteria. TTP diagnosis is based on five clinical features: reduced thrombocytopenia, microangiopathic hemolytic anemia (blood smears see broken red blood cells), nervous system abnormalities, renal damage and fever; diagnosis of TTP must have at least two criteria: microangiopathy hemolytic anemia and reduced thrombocytopenia, excluding other diseases that cause reduced thrombocytopenia and microangiopathic hemolytic anemia, such as antiphospholipid antibody syndrome and diffuse intravascular coagulation. changzhi212@163.com

2 2 VOL.1,ISS.3,DEC 2017,1-5 3.treatment programs 3.1 plasma treatment plasma infusion (PI) and (or) plasma exchange (PE). Plasma exchange volume 40-60ml / kg / d, when the patient improved symptoms it gradually adjusted to 1 time / qod, 2 times / W to 1 time / W. Plasma infusion ml / d, for 3-5 days, when the patient improved symptoms it gradually disabled. The median time to onset of plasma therapy was 2 (1-20) days, of which the median PE was 5 (1-10). 3.2 glucocorticoid treatment glucocorticoid choose methylprednisolone or prednisolone 1mg / (kg.d), or dexamethasone 10-20mg / d intravenous infusion, once every 5-14d, after stable condition the reduction and with a splash Nisong oral maintenance, specific reduction and maintenance of treatment programs is same with the diagnosis and treatment of immune thrombocytopenia [18]. 3.3 Immunosuppressant treatment 1 patient with systemic lupus erythematosus (SLE), combined with cyclophosphamide (CTX) 1.2g / w, a total of 1, due to the patients economic reasons to give up treatment, not to continue to use. 4. Efficacy: the efficacy standard reference [2-3] : 1 effective: normal platelet count, no clinical symptoms and signs; 2 some effective: PLT 50 * 10 ^ 9 / L or 1 times the basal value, no clinical symptoms and signs; 3 invalid: PLT <20 * 10 ^ 9 / L or less than 1 times, the increase in clinical symptoms; 4 recurrence: TTP clinical manifestations again after complete remission 30d. 5. Statistical analysis: The SPSS 13.0 software was used to analyze the data, and the independent sample t-test was used to compare the effective group with the death group. The difference was statistically significant at p <0.05. Other data use median representation. Results I.the clinical features 1. Causes: Nine patients with acquired TTP were acute onset, of which 3 cases co-exist autoimmune diseases, namely systemic lupus erythematosus, hyperthyroidism and immune thrombocytopenic purpura, 1 case of pulmonary infection, the rest 5 cases having no obvious incentive. 2, clinical manifestations: 9 cases of acquired TTP in patients with first symptoms include fever, thrombocytopenia, fatigue, hemolytic anemia, neuropsychiatric symptoms, the above single or joint manifestations, in the effective treatment of progressive exacerbations or successive occurrence. Five cases showed "five joint" sign. Nine patients had thrombocytopenia and MAHA, one with hemorrhage concurrently, seven with neurological symptoms, eight with fever, and five with renal insufficiency (Table 2). II.laboratory tests 1. Hematology analysis: Nine cases of TTP patients have complete blood cell analysis data. HGB median 76 (43-93) g / L, 8 cases of moderate and severe anemia; PLT median 8 (2-17) * 10 ^ 9 / L; all 9 patients with peripheral blood smear, All detected broken red blood cells, the median was 4.4% (0.5% -13.0%), of which 3 patients with broken red blood cell count 3%. 2. Biochemical tests: The countable total bilirubin values of 8 patients, the median was 76.3 ( ) μmol / L, the normal reference value ( ) μmol / L; 6 patients with median LDH 1474 ( ) U / L, the normal reference value ( ) U / L, of which 4 cases (66.67%) patients with LDH> 1000U / L. The median creatinine was 157 ( ) μmol / L in 5 patients with renal dysfunction, the normal reference value was μmol / L, the median urea nitrogen was 11.6 ( ) μmol / L, the reference value is ( ) μmol / L. 3. Plasma ADAMTS13 activity and inhibitor test: ADAMTS13 was detected in 2 of 9 patients with TTP, with 1 activity of 4.4% and 1 activity of 2.4%, meanwhile, the test result of plasma ADAMTS13 inhibitor was weakly positive. III.treatment All 9 patients received glucocorticoid therapy, of which only 1 patient was treated with glucocorticoid alone and the remaining 8 patients were treated with PE or (and) PI or (and) immunosuppressant (cyclophosphamide). One patient was accompanied by systemic lupus erythematosus. CTX 1.2g / w was used for 1 time, and then the treatment was abandoned due to economic reasons. IV. the treatment results Five patients (55.56%) died, including 3 deaths in the

3 VOL.1,ISS.3,DEC 2017,1-5 3 hospital (1 failed due to plasma therapy) and 2 patients who abandoned treatment and died outside the hospital. One patient with glucocorticoid alone died; four of the eight patients receiving plasma therapy survived and four died (Table 3). There was no significant difference in age of onset, the total bilirubin level before treatment, body temperature, white blood cell count, hemoglobin, platelet count, serum creatinine and LDH (Table 4). Discussion TTP is a rare thrombotic microvascular disease characterized by multiple systemic lesions with a prevalence of about 3.7 / 1 million [4], with a prevalence of years and a male to female ratio of about 1: 2 [5]. Recent studies of FV Leiden anomaly [14] and tissue plasminogen activator activity (t-pa) reduction [15] have been linked to the development of TTP. However, the lack of vasopressin lyase (ADAMTS13) is a major pathological mechanism of TTP [6-9], but not all TTP patients detect abnormalities of ADAMTS13, especially TTP patients secondary to other diseases can seldom detect ADAMTS13 abnormalities [10]. In this study, only 2 patients were tested for ADAMTS13 activity due to the lack of detection means or reagents, and their activity was reduced. Therefore, ADAMTS13 activity measurement is an important auxiliary indicator in the diagnosis of TTP, rather than the only standard [11], but dynamic detection of ADAMTS13 activity can provide some reference for the disease. The diversity of TTP clinical manifestations. Among the patients with acquired TTP, thrombocytopenia (100%), microangiopathy hemolytic anemia (100%) and fever (88.89%) were more common, while neurological symptoms (77.78%) and renal damage (55.56% )were relatively rare. Five cases (55.56%) had a typical "five joint sign" performance. Therefore, TTP should be considered when patients have unexplained thrombocytopenia, hemolytic anemia and fever. In addition, patients with atypical clinical manifestations, broken red blood cells and elevated LDH can also assist in the early diagnosis of TTP. Since the introduction of PE therapy in clinical practice in the 1970s, the mortality rate of TTP has been gradually reduced from 90% to 10% -20% [17]. PE is still an important method for the treatment of this disease. It can effectively remove ADAMTS13 autoantibodies and excessive vwf multimers and supplement the normal ADAMTS13 for therapeutic purposes [12]. Plasma therapy was given in 8 patients (88.89%) in this group. The median time from onset to the PE treatment was 2 (1-20) days. The clinical symptoms were significantly improved in 4 patients. The median effective time was 3 (2-4) days. The mortality rate of patients receiving plasma therapy was 50%, much higher than the lowest reported international mortality rate (4%) [13]. Possible reasons include: 1 Among the 8 patients undergoing plasma therapy, 3 gave up follow-up treatment and 1 case of poor treatment; 2 due to delayed diagnosis, not timely PE treatment or insufficient replacement. In this study, plasma therapy combined with glucocorticoid therapy in patients without recurrence and death, the plasma and hormone dose, treatment time and the drug adjustment standard is based on the actual situation of the grass-roots hospitals and patients economic conditions, the effect seems encouraging. In summary, TTP is a rare clinical critically ill, clinical complex and diverse. When patients have unexplained manifestations of thrombocytopenia and hemolytic anemia, they are indications for the initiation of TTP treatment [16]. ADAMTS13 activity detection and related biochemical indicators of dynamic changes play a guiding role for the clinical evaluation of the disease development. The advent of PE has significantly increased the survival rate of patients with TTP, especially for the elderly, winning time for the patient's life, and new therapeutic approaches for TTP are also being actively explored, mainly focusing on inhibiting the collagen-vwf-platelet response axis and VWF antibody is expected for the treatment of TTP. However, for grass-roots medical units, primary medical staff's comprehensive understanding of the disease and its familiarity with clinical features are of crucial importance for the early diagnosis of TTP. Looking for TTP treatment guidelines and emergency procedures more suitable for primary health care workers remains to be confirmed by a large number of clinical studies.

4 4 VOL.1,ISS.3,DEC 2017,1-5 Table 1 Summary of clinical data in 9 cases of acquired thrombocytopenic purpura patients no. item gender male female female female male male female male female age Body tempreture( ) WBC(*10^9/L) Hb (g/l) Plt(*10^9/L) LDH(U/L) Creatinine (umol/l) Urea nitrogen (umol/l) TB(umol/L) DB(umol/L) IB(umol/L) Ferr Re% Broken red blood cells (%) ADAMTS13 ADAMTS13 Not checked Not checked Not checked Not checked Not checked activity 2.4% Not checked Not checked 4.4% Table 2 the clinical manifestations of 9 cases of acquired thrombocytopenic purpura patients Clinical manifestations cases(%) Bleeding 6(66.67%) Cerebral hemorrhage 2(22.22%) Skin ecchymosis 3(33.33%) Menstrual volume increased 1(11.11%) Microvascular hemolytic anemia 9(100%) Neuropsychiatric symptoms 7(77.78%) Consciousness indifferent, unconscious 2(22.22%) Looking, convulsions 4(44.44%) Headache, vomiting 1(11.11%) fever 8(88.89%) Renal insufficiency 5(55.56%) Table 3 the treatment and outcome of 9 cases of thrombotic thrombocytopenic purpura patients [cases (%)] treatment method cases effective died Glucocorticoids 1 0(0) 1(100.00%) Glucocorticoids + plasma exchange + plasma infusion Glucocorticoids + plasma exchange + plasma infusion + immunosuppressants Plasma exchange + plasma infusion 3 1(33.33%) 2(66.67%) 1 0(0) 1(100%) 4 3(75.00%) 1(25.00%) Table 4 the comparison of clinical features when onset of patients with thrombotic thrombocytopenic purpura with different treatment results (± s) Clinical indicators effective group (4 cases) death group (5 cases) P value age(year) 32.25± ± body temperature( ) 39.1± ± WBC(*10^9/L) 39.8± ± HGB(g/L) 75± ± PLT(*10^9/L) 10.25± ± Total bilirubin Creatinine Urea nitrogen 78.78± ± ± ± ± ± LDH(U/L) ± ± References: [1] Chinese Society of Hematology, Department of Thrombosis and Hemostasis. Chinese expert consensus on diagnosis and treatment of Thrombotic thrombocytopenic purpura (2012 Edition) [J] Journal of Hematology, 2012,33 (11): [2] Zhan X, Streiff MB, King KE,et al. Thrombotic thrombocytopenic purpura at the Johns Hopkins Hospital from 1992 to 2008: clinical outcomes and risk factors for relapse[j]. Transfusion,2010,50(4): [3] Gurkan E, Baslamisli F, Guvenc B, et al. Thrombotic thrombocytopenic prupura in southern Turkey: a single-center experience of 29 cases[j]. Clin Lab Haematol,2003,120(4): [4] Allford SL,Hunt BJ,Rose P,et al.guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias[j].br J Haematol,2003,120(4):

5 VOL.1,ISS.3,DEC 2017,1-5 5 [5] George JN,Terrell DR,Swisher KK,et al.lessons learned from the Oklahoma syndrome registry[j].j Clin Apher,2008,23(4): [6] Zheng X,Chung D,Takayama TK,et al.structure of von Willebrand factor- cleaving protease (ADAMTS13),a metalloprotease involed in thrombotic thrombocytopenic purpura[j].j Bio Chem,2001,276(44): [7] Fujikawa K,Suzuki H,MeMullen B,et al.purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family [J].Blood, 2001,98(6): [8] Soejima K,Mimura N,Hirashima M,et al.a novel human metalloprotease synthesized in the liver and secreted into the blood:possibly,the von Willebrand factor cleaving protease?[j].j Biochem,2001,130(4): [9] SADLER J E.Von Willebrand factor,adamts13,and thrombotic thrombocytopenic purpura [J].Blood,112(1): [10] KREMER HOVINGA J A,LAMMLE B.Role of ADAMTS13 in the pathogenesis,diagnosis,and treatment of thrombotic thrombocytopenic purpura [J].Hematology Am Soc Hematol Educ Program,2012,2012: [11] George JN.How I treat patients with thrombotic thrombocytopenic purpura:2010[j].blood,2010,116(20): [12] MATSUMOTO M.Anti-ADAMTS13 autoantibodies in patientis with thrombotic thrombocytopenic purpura[j].nihon Rinsho Meneki Gakkai Kaishi,2013,36(2): [13] Zhan H,Streiff MB,King KE,et al.thrombotic thrombocytopenic purpura at the Johns Hopkins Hospital from 1992 to 2008: clinical outcomes and risk factors for relapse[j]. Transfusion,2010,50(4): [14] RAIFE TJ,LENTZ SR,ATKINSON BS,et al.faclor V Leiden;a genetic risk factor for thrombotic Microangiopathy in patients with normal von Willebrand factor-clearing protease activity[j]. Blood,2002,99(2); [15] HOIRISCH-CLAPAUCH S,NARDI AE.A role for tissue plasminogen activator in thrombotic thrombocytopenic purpura[j].med Hypotheses,2014,83(6): [16] YANG Yan,DONG Chun-xia,YANG Lin-hua.Thrombotic thrombocytopenic purpura research[j].chinese Jurnal of Thrombosis and Hemostasis,2016,22(1): [17] Bandarenko N,Brecher ME,United States Thrombotic THrombocytopenic Purpura Apheresis Study Group (US TTP ASG);multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange[j].j Clin Apher,1998,13(3): [18] Chinese Society of Hematology, Department of Thrombosis and Hemostasis. Chinese expert consensus on diagnosis and treatment of adult primary immune thrombocytopenia [J] Journal of Hematology, 2011,32 (3):