Acute pancreatitis-induced thrombotic thrombocytopenic purpura: A case report

lNTRODUCTlON

Thrombotic thrombocytopenic purpura (TTP) is a rare but fatal disease characterized by fever, thrombocytopenia, microangiopathic hemolytic anemia, renal failure, and neurological manifestations[1]. The underlying pathophysiological mechanism of TTP is deficiency or the production of antibodies against a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13).ADAMTS13 splits the ultra-large von Willebrand factor (ULVWF) polymers into smaller particles. In the absence of ADAMTS13, excess polymeric ULVWF leads to diffuse platelet-rich microthrombosis,leading to ischemia in different organs[2]. TTP-induced acute pancreatitis this mechanism is well known[3,4]. However, only a few cases of TTP as a complication of acute pancreatitis have been reported[5,6].Herein we report a case of TTP secondary to acute pancreatitis caused by a high-fat diet.

CASE PRESENTATlON

Chief complaints

2007年以來，寧夏引黃灌區采取“小步快跑、逐步到位”方式，連續2次調整農業供水價格，極大促進了水資源的可持續利用。超定額水價政策的實行，水價杠桿作用的發揮，使“水是商品”的理念深入人心。協會組織的建設，進一步提高了灌溉管理水平，支斗渠用水效率得到了大幅提升。2011年寧夏引黃灌區累計引水64.6億m3，較2005年減少7.5億m3，較實施統一調度的1999年減少23.2億m3，在全國節水型社會建設中發揮了重要的引領、帶動和示范作用。

History of present illness

由于反季節農產品價值高，大大刺激了農戶對好肥料的需求，在這里最常聽到的一句話就是“只要肥料好，價錢多少都無所謂”。因此，幾百塊錢一包（袋）的進口肥在當地非常暢銷。為讓廣大農戶用到性價比更高的國產肥料，9月底第一批反季節瓜菜進入栽種期時，新洋豐決定在東方市八所鎮小嶺村用洋豐百倍邦套餐施肥以茄子為示范作物挑戰在當地很暢銷的進口肥料。

History of past illness

The patient underwent splenectomy after an abdominal trauma three years ago, and did not undergo any follow-up.

Personal and family history

通過設置合適的門限，就能根據yr,i值判斷對應的是否屬于矩陣V的對偶空間.經分析可知，兩個分布的差異越大，識別概率越大.當時，yr,i分布主要取決于參數m和誤比特率ε，為此計算不同參數組合下兩個分布的歸一化期望差值和方差比值，即

A previously healthy 32-year-old Asian male presented to a local hospital with a 4 d history of upper abdominal pain. He had eaten some fatty food a day prior to the onset of the symptom. After 4 d of treatment at local hospital for acute pancreatitis, his abdominal pain was markedly relieved, but the blood routine showed extremely low platelets.

Physical examination

There was tenderness in the upper abdomen. No petechiae found on the skin. Heart and lung examination showed no abnormality. No masses or hepatosplenomegaly. There were no abnormal neurological signs.

There was no other relevant past medical and family histories.

Laboratory examinations

On the day of admission at the local hospital, his initial laboratory studies showed a white blood cell(WBC) count of 17.14 × 10

/L (normal 4-10 × 10

/L); neutrophils, 63.04%; lymphocytes, 31.64%;hemoglobin (HB), 152 g/L (normal 100-160 g/L); platelet count, 426 × 10

/L (normal 150-350 × 10

/L).The serum creatinine was 65 μmol/L (normal 62-106 μmol/L); blood urea nitrogen (BUN), 5.46 mmol/L(normal 1.7-8.3 mmol/L); serum amylase, 364 U/L (normal 0-100 U/L); total bilirubin, 11.5 μmol/L(normal 3.4-20.3 μmol/L), indirect bilirubin, 7.5 μmol/L (normal 0.3-16 μmol/L). After four days of treatment, the abdominal pain subsided. However, a repeat blood routine test revealed a WBC count of 13.71 × 10

/L; neutrophils, 79.21%; lymphocytes, 12.32%; HB, 104 g/L; platelet count 30 × 10

/L. Serum amylase was at 230 U/L, total bilirubin, 43.8 μmol/L, and indirect bilirubin, 21.7 μmol/L. The patient was transferred to our hospital for severe thrombocytopenia. laboratory data (day four of symptom onset) showed WBC, 12.75 × 10

/L; neutrophils, 76%; lymphocytes, 15%; HB, 102 g/L; platelets, 7 × 10

/L; urinalysis showed protein 2+, red blood cell 45/μL (normal, 0-25/μL); and stool occult blood tests were weakly positive. Coagulation studies revealed normal prothrombin time of 13.3 s (normal 9.4-12.5 s); fibrinogen, 4.76 g/L (2.38-4.98 g/L); D-dimer, 0.978 (normal 0-0.243 mg/L). Serum creatinine was 241 μmol/L; BUN, 18.5 mmol/L; serum amylase, 195 U/L; total bilirubin, 64.2 μmol/L, direct bilirubin, 8.6 μmol/L (normal 0-4 μmol/L). Lactate dehydrogenase was at 1559 U/L. There were schistocytes in his peripheral blood smear (3+; 0.5%). Both direct and indirect Coombs tests were negative (laboratory parameters showed in Table 1).

Imaging examinations

Wang CH, Jin HF and Liu WG contributed to the planning, conduction and report of the work;Wang CH and Guo Y contributed to the conception and design of the work; Wang CH and Liu Z contributed to the acquisition of analysis and interpretation of the results; All authors have read and approved the manuscript.

FlNAL DlAGNOSlS

The patient's symptoms of acute pancreatitis and abdominal pain improved. Combined with laboratory examination and abdominal computed tomography review, the thrombocytopenia caused by infection associated to acute pancreatitis was considered to be excluded. Our hospital does not have the technical platform to test for ADAMTS13. The patient’s typical laboratory data of severe thrombocytopenia with mild renal impairment were in favor of TTP over hemolytic uremic syndrome.

TREATMENT

Based on the severity of TTP, plasma exchange and intravenous methylprednisolone (40 mg/d) was initiated. After 7 sequences of plasmapheresis, oral methylprednisolone (28 mg/d) was continued.

采用光學顯微鏡和掃描電子顯微鏡分析了PFI打漿預處理對玉米芯殘渣表面形貌的影響，結果如圖1所示。從圖1可以看出，空白樣(a1和b1)的表面較為平整，受損情況較弱，輪廓邊界規整，有明顯顆粒狀外形；而經過PFI打漿后(a2和b2)，玉米芯殘渣的表面變得粗糙，表面分絲起毛，并產生少量細小碎片，輪廓邊界變得不規則，無明顯顆粒狀外形；當打漿轉數達到20000轉時，玉米芯殘渣(a3和b3)的表面破損情況嚴重，幾乎完全壓潰變形，并產生了大量的細小碎片。

OUTCOME AND FOLLOW-UP

After 7 sequences of plasmapheresis, the patient’s platelet count increased to 147 × 10

/L, and urea,creatinine, and HB returned to normal (laboratory parameters showed in Table 1). Plasma exchange was stopped and oral methylprednisolone (28 mg/d) was continued. The patient was discharged 13 d after admission. Discharge follow-up showed recurrent pancreatitis 8 mo later without TTP. Due to coronavirus disease 2019 and his condition improved, the patient was not able to complete the test for ADAMTS13.

A 32-year-old male presented with an 8 d history of upper abdominal pain and thrombocytopenia was observed for 1 d.

DlSCUSSlON

TTP is a rare disease with an annual incidence of approximately 6 per 1 million[7]. It can be congenital or acquired by any cause of ADAMTS13 deficiency or dysfunction of the ADAMTS13 enzyme. Acquired TTP is usually due to autoantibodies that inhibit ADAMTS13 activity and impair ULVWF function. TTP usually manifests as an acute and fulminant, sometimes fatal process. However, acute inflammatory disease has been known to reduce the activity of ADAMTS13[8].

功率參數設計方案 用大信號頻帶完全覆蓋機密信號頻帶，同時設計大信號和機密信號的功率參數滿足Ps/Pw≥η0，η0表示能夠保證機密信號抗盲檢測的最小功率比值.

TTP, a life-threatening disorder, is sometimes caused by acute pancreatitis. TTP is a rare and serious complication of acute pancreatitis. Therefore, when TTP is highly suspected clinically but cannot be diagnosed early, prompt plasmapheresis and glucocorticoid therapy are necessary and may lead to a favorable outcome.

Due to the high fatality rate of TTP, diagnostic treatment is initiated before more definitive test results such as ADAMTS13 Levels can be obtained. Before the 1980s, prior to the era of therapeutic plasmapheresis for TTP, the fatality rate was greater than 90%[13]. Treatment includes immediate and daily therapeutic plasmapheresis with oral or intravenous glucocorticoids, depending on the patient’s neurological status. Because the platelet count reflects the disease’s response to treatment, it should be monitored daily. Once the platelet count exceeds 150000/mL for more than 2 d, therapeutic plasma-pheresis can be discontinued and steroid therapy continued. When the platelet count is stable, steroids can be reduced while the platelet count continues to be monitored[14].

About 40% of patients with TTP are likely to experience a relapse[15]. One study found a recurrence rate of about 36% during a 30-mo follow-up period, with about 76% occurring within the first 24 mo[16]. Splenectomy remains a viable, but non-curative, treatment option for patients with recurrent or refractory disease. In a case series by Dubois and Gray, patients who underwent splenectomy for recurrent TTP had better outcomes than patients who underwent splenectomy for refractory disease.They noted that in the recurrent TTP group and the refractory group that underwent splenectomy, the overall complication rate was 6% and 10%, respectively, and the mortality rate was 1.2% and 5%,respectively. In addition, they found that the recurrence rate of TTP after splenectomy was about 17%[17]. It has been suggested that splenectomy may benefit patients with TTP because it removes a large number of B lymphocytes that produce pathogenic autoantibodies. By eliminating the source of pathogenic autoantibody production, splenectomy can be a successful treatment option for patients with recurrent or plasma refractory acquired TTP due to autoantibody mediated defects in ADAMTS13[18]. However, in the present case, the patient underwent splenectomy three years previously, and in the absence of a spleen, the patient still had a recurrence of acute pancreatitis at eight months follow-up albeit without being complicated with TTP. However, more follow-up in the future is required to examine whether TTP will relapse.

古詩文是五千年中華文明的積淀，她博大精深，源遠流長，是傳統文化的瑰寶，她因凝練含蓄的語言、深邃雋永的意境而深受人們的喜愛。她能開闊學生的眼界，豐富學生的知識，撞擊學生的靈魂，滋養學生的性情，她讓學生感受和體驗到各種文化現象背后所蘊藏的深層的文化、精神文化情感。她是中華民族優于其它民族的力量源泉。

CONCLUSlON

Pancreatic injury caused by TTP is common, the mechanism of TTP-induced pancreatic injury is believed to be the pancreatic circulation disturbance caused by thrombus occlusion of small vessels[9].Only a few cases of TTP as a complication of acute pancreatitis have been reported. Acute pancreatitis is an inflammatory disease characterized by tissue damage in situ. Increased levels of cytokines including interleukins (IL-8, IL-1, and IL-6) and tumor necrosis factor (TNF-α) may stimulate the release of ULVWF by endothelial cells. This may account for the relative deficiency of the ADAMTS13 protease in acute pancreatitis, which is rapidly consumed. Acute pancreatitis mediated TTP typically occurs within 1 to 13 d (median 3 d) of the diagnosis of acute pancreatitis, possibly due to the peak levels of inflammatory cytokines IL-6 and IL-8 on the 3 d after the onset of pancreatitis[10]. Nitric oxide may also be involved in the development of TTP after acute pancreatitis[11].

studies have shown that inflammatory factors stimulate the release of ULVWF from endothelial cells and inhibit the cleavage of ULVWF by ADAMTS13[12].

FOOTNOTES

Abdominal computed tomography revealed signs of pancreatitis (Figure 1).

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

No potential conflicts of interest relevant to this article were reported.

The authors have read the CARE Checklist (2016) and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

國內已有學者進行相關調查。蔡基剛(2010)在復旦大學對學生進行訪談，接受訪談的學生表示一下子從基礎英語進入以專業知識為教學重點、由外教開設的全英語專業課程，感到無所適從，希望在上全英語專業課前有一門銜接性課程，幫助他們過渡到以英語為媒介的專業課程學習。何宇茵等(2007)對北京航空航天大學上雙語課的學生進行訪談也有類似結果：“學生建議是改良大學英語課程，在大學英語中融入簡單的專業知識，這樣既學了英語，也對專業知識有所裨益。或在大學英語和專業英語課之間開一門過渡性課程，講授一些科技英語的文體特點和語言習慣表達法”。

China

Chun-Hua Wang 0000-0002-2352-8874; Hai-Feng Jin 0000-0002-9089-2799; Wen-Ge Liu 0000-0003-3451-5267; Ying Guo 0000-0002-0535-0101; Zhen Liu 0000-0002-7755-5093.

Zhang H

A

Zhang H

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