Effectiveness of total therapy in immune thrombocytopenia purpura:case series

Immune Thrombocytopenic purpura(ITP)is a haematologicimmune-mediated disorder in which the amount of platelet in the blood decreases abnormally.Single-agent therapies for ITP have not proven successful in achieving long-term remission,with relapse occurring in about half of the patients(p/t).Treatment options which include Rituximab with Dexamethasone as frontline therapy,have durable response rates ranging from 58%to 76%.In this study,we have used‘Total therapy’as treatment which includes low-dose Rituximab in combination with Thrombopoietin receptor agonist(TPO-RA)(Romiplostim)and high-dose Dexamethasone.In this case series study,each patient received romiplostim(250 mcg weekly s/c,4 doses)in combination with low-dose rituximab(100 mg weekly IV,4 doses)and high-dose dexamethasone(40 mgIV on days 1-4and days 15-18).This treatment combination demonstrated rapid response rates and a low rate of side effects,making it a good alternative for individuals with ITP.

Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection

We report the first case of a patient with hepatitis C virus(HCV) infection and idiopathic thrombocytopenic purpura(ITP), who later developed acquired amegakaryocytic thrombocytopenia(AAMT), with autoantibodies to the thrombopoietin(TPO) receptor(c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.

Immune Thrombocytopenia Purpura (ITP) with Grave’s Disease, in a Plasmodium Vivax Positive Patient. A Case Report

Hyperthyroidism and thrombocytopenia have long been associated with each other. We present a case of 38 years old female presenting with complaints of bleeding from gums, bleeding per rectum, hematuria and easy bruising since 7 days ago. She also had a diffuse, non-tender neck swelling moving with deglutition and positive bruit on auscultation. Her laboratory results indicated thrombocytopenia (22 × 10^9/L) and her thyroid function test revealed TSH of 0.01 mIU/ml (normal: 0.17 - 4.05), free T3 of 19.19 pg/ml (normal: 1.6 - 3.7), free T4 of 4.09 ng/dl (normal: 0.89 - 1.79). Thyroid scan showed diffuse goiter with increased tracer uptake. Furthermore, her serum anti-thyroglobulin and anti-thyroid peroxide were elevated to 205 IU/ml and 713 IU/ml respectively. She was started on carbimazole and methylprednisolone immediately. On the 3rd day of admission, she was tested to be positive for Plasmodium Vivax after a fever spike and was started on Chloroquine (CQ) and later shifted to Primaquine (PQ). During 2 weeks of admission, her platelet count kept fluctuating between <10 × 10^9/L and <100 × 10^9/L with frequent transfusions of mega units of platelets. During 3rd week, her platelets improved and she was discharged with a platelet count of 370 × 10^9/L. This case, therefore, supports the association between autoimmune thyroid diseases such as Graves’ disease and idiopathic thrombocytopenic purpura (ITP) strongly suggesting the need for evaluating thyroid disease in cases of severe thrombocytopenia especially those refractory to treatment. Also, the effectiveness of treatment of thyroid disease on thrombocytopenia is also highlighted. In addition, it showed the possible added exacerbating effects of malarial infection on thrombocytopenia.

New mechanisms of the TCM spleen-based treatment of immune thrombocytopenia purpura from the perspective of blood neurotransmitters

Objective:To explore new mechanisms of the traditional Chinese medicine (TCM)spleen-based treatment of immune thrombocytopenic purpura (ITP) from the perspective of blood neurotransmitters.Methods:In this randomized controlled multi-center clinical study,271 ITP patients who met the diagnostic criteria of 'syndrome of spleen failing to manage blood' were randomized into three groups:group A administered Jianpi Yiqi Shexue (JYS) granules,1 bag per treatment,bid;group C administered prednisone as a draught at an initial dose of 1.0-1.5 mg/kg/day at 8:00 AM;and group B administered a combination of the interventions in groups A and C.Each treatment cycle lasted 21 days.Results:After treatment,scores of platelet distribution width (PDW) were significantly decreased in groups B and C,and there were significant differences among the three groups (P =.0131).Pairwise comparisons showed that PDW was significantly different between group A and group B (P =.005) and between group A and group C (P =.041) but not between group B and group C.Hemorrhage grading scores were significantly different between day 1 and day 7 in group A and group B (P <.001) but not in group C.The hemorrhage grading scores on day 14 and day 21 were significantly different from that on day 1 in all three groups (P <.001).Serum 5-hydroxytryptaminelevels did not change significantly before and after treatment in the three groups (P >.05).Serum β-endorphin and vasoactive intestinal peptide levels were significantly different between group A and group B (both P <.001).Conclusions:The JYS prescription may regulate the expression levels of blood neurotransmitters via the brain-gut axis in patients with 'spleen deficiency' ITP and thus activate hemostatic mechanisms to promote hemostasis.β-EP and VIP are key neurotransmitters of the JYS-induced functional regulation.

Dermatoscope for the diagnosis of erythema with purpura induced by lidocaine/prilocaine cream:A case report

BACKGROUND Lidocaine/prilocaine(EMLA)cream is a local anesthetic that is applied to the skin or mucosa during painful therapeutic procedures with few reported side effects.CASE SUMMARY Here,we report the use of dermatoscopy to identify a case of erythema with purpura,a rare side effect,after the application of 5%EMLA cream.CONCLUSION We conclude that erythema with purpura is caused by irritation and toxicity associated with EMLA,but the specific mechanism by which the toxic substance affects skin blood vessels is unclear.In response to this situation and for cosmetic needs,we recommend tranexamic acid,in addition to routine therapy,to prevent changes in pigmentation in patients with dermatitis.

Thrombotic Thrombocytopenic Purpura in Pregnancy Presented with Stroke at 29 Weeks: A Case Report

Thrombotic thrombocytopenic purpura (TTP) is a rare but acute, life-threatening condition which may be precipitated by pregnancy. This disorder that presents with thrombocytopenia, haemolytic anemia, and clinical consequences of microvascular thrombosis such as stroke. The exact cause is not known but it is associated with a deficiency of ADAMTS13 enzymes. Immune mediated TTP is more common and can present in pregnancy. The aim of this case is to bring awareness as many clinicians are unaware of this condition in pregnancy, its diagnosis may be missed or delayed, leading to fetal loss or serious maternal implications. In this case the patient presented at 29 weeks with stroke in Emergency department, referred to delivery suit for Obstetric review, with suspicion of Pre-eclampsia/HELLP. The diagnosis of TTP was achieved by a multidisciplinary team who worked tirelessly together. The patient was transferred to a Specialist Tertiary Care Centre for further management. The pregnancy continued until 33 weeks and 5 days. She underwent an emergency caesarean section for fetal distress. Steroids and Rituximab were continued postnatally. The outcome was favourable due to fast and efficient multidisciplinary care. Awareness of this rare but important condition can lead to recognition of clinical presentation, prompt diagnosis and appropriate management.

Periorbital purpura can be the only initial symptom of primary light chain amyloidosis:A case report

BACKGROUND Primary light chain amyloidosis is a rare and complex disease with complex clinical features and is highly susceptible to misdiagnosis and underdiagnosis in the early stages.CASE SUMMARY We report a case of a 47-year-old female patient whose only initial symptom was periorbital purpura,which was not taken seriously enough.As the disease progressed,pleural effusion gradually appeared,and after systematic diagnosis and treatment,she was diagnosed with“primary light chain amyloidosis”.She achieved rapid hematological remission after treatment with a daratumumab+bortezomib+cyclophosphamide+dexamethasone regimen.CONCLUSION Periorbital purpura can be the only initial symptom of primary light chain amyloidosis;we should pay attention to the cases where the initial clinical symptoms are only periorbital purpura.

A Case of Investigation and Diagnosis of Immune Thrombocytopenic Purpura After Vaccination of COVID-19 Inactivated Vaccine

Objective:Analyze the relationship between inoculating one case of the COVID-19 inactivated vaccine(Vero cell)and immune thrombocytopenic purpura to provide a reference for the standardized handling of adverse events following immunization.Methods:According to the"National Monitoring Program for Suspected Adverse Reactions to Vaccinations,"an on-site investigation,data collection and analysis,expert group diagnosis,and medical association assessment were conducted on a case of immune thrombocytopenic purpura in District A of Chongqing after vaccination with the inactivated COVID-19 vaccine.The assessment report was delivered to the three relevant parties,the case was reviewed,and the experience was summarized.Results:The investigation and diagnosis by the district-level vaccination abnormal reaction expert group concluded that the disease that occurred after vaccination with the COVID-19 inactivated vaccine was secondary immune thrombocytopenic purpura,an abnormal reaction to the vaccination.The medical damage was classified as Level II Grade B.The vaccine production enterprise raised objections to this conclusion.After re-assessment by the municipal-level medical association,the conclusion was consistent with that of the district-level medical association.The vaccine production enterprise did not raise any further objections.Conclusion:Through active collaboration among district and municipal-level medical associations,disease control institutions,and vaccination units,the recipients have been promptly and effectively treated,providing financial support for their subsequent treatment and safeguarding their rights.The investigation and disposal procedures for adverse events following immunization in Chongqing are clear,and the mechanism is sound.It is necessary to continue strengthening the monitoring of adverse events following immunization according to the existing plan and to ensure timely and standardized handling.Simultaneously,it is crucial to strengthen vaccine management and vaccination management.

Albumin–bilirubin grade as a predictor of survival in hepatocellular carcinoma patients with thrombocytopenia

BACKGROUND The models for assessing liver function,mainly the Child–Pugh(CP),albuminbilirubin(ALBI),and platelet–ALBI(PALBI)classifications,have been validated for use in estimating the prognosis of hepatocellular carcinoma(HCC)patients.However,thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC.AIM To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients.METHODS A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed.Preoperative scores on the CP,ALBI and PALBI classifications were estimated accordingly.Kaplan–Meier curves with logrank tests and Cox regression models were used to explore the significant factors associated with overall survival(OS)and recurrence-free survival(RFS).RESULTS The preoperative platelet counts were significantly different among the CP,ALBI and PALBI groups.After a median follow-up of 28 mo,39.3%(53/135)of the patients experienced postoperative recurrence,and 36.3%(49/135)died.Univariate analysis suggested thatα-fetoprotein levels,tumor size,vascular invasion,and ALBI grade were significant predictors of OS and RFS.According to the multivariate Cox regression model,ALBI was identified as an independent prognostic factor.However,CP and PALBI grades were not statistically significant prognostic indicators.CONCLUSION The ALBI grade,rather than CP or PALBI grade,is a significant prognostic indicator for thrombocytopenic HCC patients.

Diagnostic Approach of Thrombocytopenia in Pregnancy: A Review

Thrombocytopenia (defined as platelet count 9/L) is present in 7% - 12% of pregnant women at delivery. Although there are mild etiologies of this condition that are often diagnosed incidentally, there are more severe causes that can be life threating. Thrombocytopenia also has a great implication in surgical risk and regional anesthesia. A structured evaluation of thrombocytopenia is necessary to allow an adequate diagnostic approach. Here we summarized the current knowledge of thrombocytopenia in pregnancy.

Predictive value of thrombocytopenia for bloodstream infection in patients with sepsis and septic shock

BACKGROUND Thrombocytopenia is common in patients with sepsis and septic shock.AIM To analyse the decrease in the number of platelets for predicting bloodstream infection in patients with sepsis and septic shock in the intensive care unit.METHODS A retrospective analysis of patients admitted with sepsis and septic shock in Xingtai People Hospital was revisited.Patient population characteristics and laboratory data were collected for analysis.RESULTS The study group consisted of 85(39%)inpatients with bloodstream infection,and the control group consisted of 133(61%)with negative results or contamination.The percentage decline in platelet counts(PPCs)in patients positive for pathogens[57.1(41.3-74.6)]was distinctly higher than that in the control group[18.2(5.1–43.1)](P<0.001),whereas the PPCs were not significantly different among those with gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.Using receiver operating characteristic curves,the area under the curve of the platelet drop rate was 0.839(95%CI:0.783-0.895).CONCLUSION The percentage decline in platelet counts is sensitive in predicting bloodstream infection in patients with sepsis and septic shock.However,it cannot identify gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.

Angiotensin II administration in severe thrombocytopenia and chronic venous thrombosis:A case report

BACKGROUND The initial trials on angiotensin II(AT II)administration indicated a high incidence of thrombocytopenia and thrombosis,as well as a positive correlation between hyperreninemia and response to the medication.CASE SUMMARY We describe a case of a patient presenting with catecholamine resistant septic shock,thrombocytopenia,deep vein thrombosis,and normal renin concentration who responded immediately to AT II treatment.We observed no worsening of thrombocytopenia and no progression of thrombosis or additional thromboses during treatment.CONCLUSION Our case underscores the need for individualized assessment of patients for potential therapy with AT II.

Endoscopic findings in a patient with Henoch-Schonlein purpura

Henoch-Schonlein purpura (HSP) is a systemic vasculitis of the small vessels of the skin, joints, GI tract, and kidney. It preferentially affects children but may also occur in adults. We report a 60-year-old man with HSP who presented with colicky abdominal pain, bloody diarrhea, arthralgia, and skin rash. The gastrointestinal tract was viewed by upper endoscopy and colonoscopy. We found characteristic endoscopic findings in the stomach, cecum and sigmoid colon, the combination of which has rarely been demonstrated in one patient. Histologic examination of skin biopsy specimens revealed leukocytoclastic vasculitis with positive staining for IgA in the capillaries. Endoscopy appears to have substantial diagnostic utility in patients suspected of having HSP, especially when abdominal symptoms precede the cutaneous lesions.

Helicobacter pylori-associated immune thrombocytopenia:Clinical features and pathogenic mechanisms

Immune thrombocytopenia (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. There is growing evidence that the eradication of Helicobacter pylori (H. pylori) effectively increases platelet count in a considerable proportion of ITP patients infected with this bacterium. In the majority of ITP patients responding to H. pylori eradication therapy, the anti-platelet autoantibody response is completely resolved with no relapse for more than 7 years, indicating that the disease is cured. Therefore, adult patients with suspected ITP should be examined for H. pylori infection, and eradication therapy is recommended if the infection is present. Notably, however, the efficacy of H. pylori eradication therapy in ITP patients varies widely among countries, with a higher response rate in Japan compared with the United States and European countries other than Italy. The pathogenesis of H. pylori-associated ITP is still uncertain, although the mechanisms are known to involve multiple factors. H. pylori may modulate the Fc&#x003b3;-receptor balance of monocytes/macrophages in favor of activating Fc&#x003b3; receptors, and H. pylori components may mimic the molecular makeup of platelet antigens. Further studies of the pathogenic process of H. pylori-associated ITP may be useful for the development of new therapeutic strategies for ITP.

Heparin-induced thrombocytopenia in solid organ transplant recipients: The current scientific knowledge

Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on antiheparin/PF4 antibodies and HIT in transplant recipients a systematic Pub Med literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.

Identification of 8 Rare Deleterious Variants in ADAMTS13 by Next-generation Sequencing in a Chinese Population with Thrombotic Thrombocytopenic Purpura

Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.

Immune thrombocytopenia in adults

Immune thrombocytopenia is an autoimmune disease resulting in the destruction of platelets.It is classified as acute,thrombocytopenia occurring for < 6 mo and usually resolving spontaneously,and chronic,lasting >6 mo and requiring therapy to improve the thrombocytopenia.The underlying defects leading to autoantibody production are unknown.Molecular mimicry appears to play a role in the development of self-reactive platelet antibodies after vaccination and certain viral infections.Platelet life span is reduced as a consequence of antibody-mediated clearance by tissue macrophages in essentially all patients.Diagnosis is based on the exclusion of the other causes of thrombocytopenia.Steroid is the first choice of the treatment,often followed by splenectomy in unresponsive cases.Intravenous immunoglobulin,anti-Rho(D) immune globulin,azathioprine,cyclosporine A,cyclophosphamide,danazol,dapsone,mycophenolate mofetil,rituximab,thrombopoietin receptor agonists and vinca alkaloids are other choices of treatment.

Establishment of a Mouse Thrombocytopenia Model Induced by Cyclophosphamide

An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route that could cause stable thrombocytopenia. A suitable drug dosage that could induce thrombocytopenia in mouse efficiently with the definite administration route was then investigated. BALB/c mice were randomly divided into Normal, Model A and Model B groups. To Model A, 200 mg/kg of cyclophosphamide was given by vena caudalis injection as first dose and 30 mg/kg as maintenance dose by intraperitoneal injection at the following 6 days. To Model B, 150 mg/kg of cyclophosphamide was given by subcutaneous injection once a day for consecutive 3 days. All groups were under investigation for 15 days. The result suggested that a decrease in the number of blood platelets of Model B at the 7th day were significantly than that of Normal. Other platelet related indices like platelet distribution width, mean platelet volume and platelet-large cell ratio of Model B increased significantly in comparison with those of Normal group. The platelets count was reduced but fluctuated greatly, and more than half of the mice died in Model A. Therefore, subcutaneous injection of cyclophosphamide for 3 days was used for the cyclophosphamide dosage test. BALB/c mice were randomly divided into Normal, cyclophosphamide low dose （100 mg/kg）, medium dose （120 mg/kg） and high dose （140 mg/kg） groups. All groups were under investigation for 11 days. Though all 3 dosages successfully initiated thrombocytopenia as the platelets number dropped at the 7th day, the low dose was considered to be a suitable one that was of high efficacy and low toxicity. Thus, BALB/c mice challenged by subcutaneous injection of cyclophosphamide 100 mg/kg per day for 3 consecutive day is one simple, feasible and stable mouse thrombocytopenia model that could be used for pharmacodynamic test of the drugs which are supposed to have platelets increasing effect.

Successful Treatment of Severe Heparin-induced Thrombocytopenia with Intravenous Immunoglobulin, Platelet Transfusion and Rivaroxaban: A Case Report

Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.

Henoch-Schonlein purpura with intestinal perforation and cerebral hemorrhage: A case report

Henoch-Schonlein purpura (HSP) with intestinal perforation and cerebral hemorrhage is a very rare clinical condition. There has been no report of HSP complicated with both intestinal perforation and cerebral hemorrhage until October 2012. Here we describe a case of HSP with intestinal perforation and cerebral hemorrhage in a 5-year-old girl. Plain abdominal radiograph in the erect position showed heavy gas in the right subphrenic space with an elevated diaphragm. Partial resection of the small intestine was performed, and pathological analysis suggested chronic suppurative inflammation in all layers of the ileal wall and mesentery. Seventeen days after surgery, cerebral hemorrhage developed and the patient died.