Treatment Of Thrombocytopenic Purpura Research Articles

Types of plasma exchange solution in the new scenario of thrombotic thrombocytopenic purpura treatment.

Types of plasma exchange solution in the new scenario of thrombotic thrombocytopenic purpura treatment.

Use of n-acetylcysteine therapy in patients with relapsed refractory thrombotic thrombocytopenic purpura

There is limited data on the use of NAC in the literature. We would like to present the satisfactory results we obtained in our resistant and relapsed patients as a case series.Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy caused by ADAMTS13 (a disintegrin with thrombospondin type 1 motif and metalloprotease activity, member13) deficiency. Von Willebrand factor (vWF) initiates platelet aggregation and thus thrombus formation. The multimers of vWF are cleaved by ADAMTS13. Because of the decreased activity of ADAMTS13, ultra-large multimers accumulate and end-organ damage occurs. TTP is characterized by microangiopathic hemolytic anemia (MAHA), severe thrombocytopenia, and organ ischemia resulting from vascular occlusion caused by thrombi. Plasma exchange therapy (PEX) remains the mainstay of TTP therapy. Patients who do not respond to PEX and corticosteroids require additional treatments such as rituximab and caplacizumab. NAC reduces disulfide bonds in mucin polymers through its free sulfhydryl group. Thus, the size and viscosity of the mucins are reduced. VWF is structurally similar to mucin. Based on this similarity, Chen and colleagues showed that NAC can reduce the size and reactivity of ultralarge multimers of vWF, such as ADAMTS13. Currently, there is not much information to suggest that NAC has any clinical value in the treatment of TTP. In this case series of 4 refractory patients, we would like to present the responses we obtained with the addition of NAC therapy. NAC can be added to PEX and glucocorticoid therapy as supportive therapy, especially in unresponsive patients.

The traditional Chinese medicine (TCM), Sheng-xue-xiaoban, inhibits the angiogenesis in ovarian cancer in vitro

Purpose: The traditional Chinese medicine (TCM), Sheng-xue-xiao-van (SXXB) is reported to be effective in treatment of thrombocytopenic purpura and chemotherapy-induced thrombocytopenia in clinical practices. The purpose of this study was to explore the functions of the SXXB Capsule in ovarian cancer in vitro.Methods: The toxicity of the medicine was measured using CCK8 method in ovarian cancer cell lines A2780 and OC-3-VGH and also the human ovarian epithelial cell line IOSE80. The cells were treated using the DMSO-diluted SXXB solution with the concentration levels at0, 3.125 and 6.25 μg/ml. Western blot was applied to measure the VEGFA proteins in each group. Later, the cells treated with 0 and 25μg/ml SXXB solution for 48h were collected for supernatant. Then HUVECs were co-cultured with the supernatant. Migration and tube formation assays were performed thereafter.Results: SXXB solution showed higher toxicity in ovarian cancer cells than in IOSE80. The protein levels of VEGFA were reduced as the SXXB concentrations increased in ovarian cancer cells but not in IOSE80. Migration and formed tubes were inhibited in HUVECs co-cultured with the supernatant collected from SXXB-treated ovarian cancer cells.Conclusion: The SXXB Capsule might inhibit the angiogenesis in ovarian cancer in vitro.

European Renal Best Practice endorsement of guidelines for diagnosis and therapy of thrombotic thrombocytopaenic purpura published by the International Society on Thrombosis and Haemostasis.

ABSTRACTThrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that is caused by severe ADAMTS-13 deficiency. Immune-mediated TTP develops due to autoantibodies against ADAMTS-13, whereas congenital TTP is caused by mutations in the ADAMTS13 gene. Diagnostic possibilities and treatment options in TTP have emerged in recent years, which prompted the International Society on Thrombosis and Haemostasis (ISTH) to publish clinical practice guidelines for the diagnosis and treatment of TTP in 2020. In this article, the European Renal Best Practice Working Group endorsed the ISTH guidelines and emphasizes a number of considerations, including the importance of rapid ADAMTS-13 activity testing, the use of rituximab and anti-von Willebrand factor therapies such as caplacizumab, that enhance the clinical applicability of the guidelines in Europe.

RETRACTED: Two-fold interpenetrated Cd(II) compound: Photocatalytic property and application values on persistent thrombocytopenic purpura

• A new Cd(II) compound, [(CH 3 ) 2 NH 2 ][Cd 2 (INA)(pdc) 1.5 (ad)] n •2n(H 2 O) ( 1 ) has been prepared. • Compound 1 exhibits excellent photocatalytic activity for the degradation of methylene blue (MB) under UV light illumination. • The biological activity of the new compound on the persistent thrombocytopenic purpura was evaluated. A new Cd(II) compound, [(CH 3 ) 2 NH 2 ][Cd 2 (INA)(pdc) 1.5 (ad)] n ·2n(H 2 O) ( 1 ) has been prepared by introducing terephthalic acid (H 2 pdc) and isonicotinic acid (HINA) to assemble with adenine (Had) and Cd(NO 3 ) 2 ·4H 2 O. The investigation of photocatalytic property shows that compound 1 exhibits excellent photocatalytic activity for the degradation of methylene blue (MB) under UV light illumination. Its biological activity on the persistent thrombocytopenic purpura treatment was evaluated and the related mechanism was explored at the same time. Firstly, the relative expression levels of HPA-2 on platelets in the persistent thrombocytopenic purpura animal after compound treatment was measured with real time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Besides, the Annexin V-FITC Apoptosis Detection was performed to measure the levels of the platelets in the persistent thrombocytopenic purpura animal after compound treatment.

Biosimilar of Rituximab for the Treatment of Primary Immune Thrombocytopenic Purpura : A Case-Control Study

INTRODUCTION Despite their daily use in the treatment of Thrombocytopenic Purpura Immunologic (ITP), rituximab biosimilars have never been evaluated directly in this indication. Our objective was to compare the efficacy and the tolerance of Rixathon ©, systematically used in our structure since April 2018, Mabthera © at adult patients with primary ITP. PATIENTS AND METHODS Medical records of the patients treated with Rixathon © for a primary ITP in our structure until December 31, 2019 have been retrospectively analyzed. All of these patients were included in the safety analysis. Patients with ITP secondary to an active malignant hematologic condition, a well-established auto-immune systemic disease or an anti-phospholipid syndrome, as well as patients in whom another ITP treatment was introduced within 8 weeks before or after the first injection of biosimilar, were excluded from the efficacy analysis. Rituximab-naive patients and those who had already received it in the past were separated into two groups. Naive patients were compared with controls from the registry "ITP-Ritux "which contains data from 248 patients treated with Mabthera © for a primary ITP. Rituximab non-naive patients were their own control. For the efficacy analysis, the primary endpoint used was the initial response to treatment, defined according to international criteria. A complete response corresponded to a platelet count> 100 G / L, a partial response to a level> 30 G / L with a doubling of the platelet count from the level before the injection. All other situations were considered as failures. For the safety analysis, all side effects, whether immediate or delayed, were collected. RESULTS A total of 38 patients treated with Rixathon © for ITP were included in the safety analysis. Of these patients, 26 (68%) were rituximab naïve and 6 (16%) had secondary ITP. The majority of patients were women (n = 28, 74%). Most of them were in the chronic stage of ITP (n = 24, 63%). Only 2 (5%) of the patients had undergone splenectomy. The median duration of follow-up was 6 months [IQR 3-12.5 months]. Of the 22 naive patients included in the efficacy study, 7 (32%) had a complete response and 8 (36%) a partial response. The observed overall response rate was 68%, a rate comparable to that observed in the PTI-Ritux registry (61%). In the 10 non-naïve rituximab patients included in the efficacy analysis, 6 (60%) were in complete response and 2 (20%) in partial response, i.e. an overall response rate of 80% in patients who had previously all responded favorably to Mabthera ©. During follow-up, 6 (16%) patients required initiation of at least one other disease-modifying treatment for ITP. Regarding immediate tolerance, 3 (8%) patients had immediate side effects when starting treatment but none required stopping the infusion: one patient presented with hives, another with abdominal pain and finally a patient was hospitalized after the infusion for a flare-up of heart failure. Away from the infusion, transient deep neutropenia was observed in 2 of 12 patients who were not rituximab naive. One of these two patients developed sepsis requiring hospitalization. In addition, during follow-up, one patient presented with pulmonary embolism and another with chronic abdominal pain. CONCLUSION The short-term efficacy of Rixathon © appears to overlap with that of Mabthera © in the treatment of primary ITP in adults. Data on a larger scale, with a more prolonged follow-up, are being collected in order to confirm these encouraging data. Disclosures Mahevas: GSK:Research Funding.Michel:Alexion Pharmaceuticals:Consultancy;Bioverativ:Consultancy;Rigel:Consultancy.Godeau:LFB:Honoraria;Novartis:Honoraria;Amgen:Honoraria;Amgen:Research Funding.

Idiopathic thrombocytopenic purpura treatment in a relapsed/refractory multiple myeloma patient after chimeric antigen receptor T cell therapy.

The adoptive transfer of CAR-T cells, which are modified T cells expressing chimeric antigen receptors (CARs), to target B cell maturation antigen (BCMA) has demonstrated impressive results in treating relapsed/refractory multiple myeloma. Although BCMA CAR-T therapy induces certain complications in some patients, idiopathic thrombocytopenic purpura (ITP) has not been reported as one of them. To the best of our knowledge, this is the first report of the successful treatment of ITP that arose in a relapsed/refractory multiple myeloma patient following anti-BCMA CAR-T cell infusion. Herein, we describe this relatively uncommon complication and provide guidance on its treatment.

Methylene blue-treated plasma, versus quarantine fresh frozen plasma, for acute thrombotic thrombocytopenic purpura treatment: Comparison between centres and critical review on longitudinal data

IntroductionTherapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial.Patients and methods: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. ResultsDuring the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). ConclusionMBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.

Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment

ABSTRACTIntroduction: Immune thrombotic thrombocytopenic purpura (iTTP) is an immune-mediated deficiency in von Willebrand factor-cleaving protease ADAMTS13 allowing unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis. Caplacizumab, an anti-von Willebrand factor humanized, bivalent single-domain nanobody preventing its binding to the platelet has been investigated and approved for use in the treatment of iTTP.Areas covered: The purpose of this article is to summarize the available clinical data on the efficacy and safety of caplacizumab in iTTP and to provide our opinion on the place of caplacizumab in current treatment regimens.Expert opinion: Caplacizumab is a new drug with a complementary mechanism of action with respect to the standard available therapeutics. It demonstrated efficacy in clinical trials through a faster platelet count normalization and protection of patients from exacerbations and refractoriness. Caplacizumab is well tolerated with minor bleeds as the most important side effect. The efficacy of caplacizumab now needs to be assessed in real-life but definitely, this drug opens hope for a significant improvement in iTTP prognosis at the very early, critical step of the disease.Trial registration: ClinicalTrials.gov identifier: NCT03922308.Trial registration: ClinicalTrials.gov identifier: NCT02553317.

Comparison of ADAMTS13 and Von Willebrand factor levels and activities, and plasminogen levels, in plasma products currently available for the treatment of thrombotic thrombocytopenic purpura in South Africa

ObjectiveThrombotic thrombocytopenic purpura (TTP) results from a deficiency in the Von Willebrand factor (VWF) cleaving protease, ADAMTS13. Treatment involves plasma exchange (PEX) therapy with either fresh frozen plasma (FFP), cryosupernatant (CSP) or solvent/detergent-treated plasma (SDP), available in South Africa as Bioplasma FDP. The aim of the study was to generate in vitro data on these products, and to explore possible differences between the products that may offer treatment advantages. MethodsTwenty samples per product (FFP, CSP and Bioplasma FDP) were analysed for levels and activities of ADAMTS13 and VWF. Plasminogen levels, a proposed physiological back-up system for ADAMTS13, were also determined. FFP and CSP samples were subanalysed according to ABO blood group. Samples were analysed by means of commercially available ELISA assays. ResultsAll samples had normal/high ADAMTS13 activity (Median activity for SDP = 94.0%, CSP = 80.5%, FFP = 122.0%) and plasminogen levels. The VWF content was mostly normal for Bioplasma FDP, typically deficient for CSP and mostly deficient for FFP, which was an unexpected finding. Depending on the parameter, Bioplasma FDP was the most standardised, with coefficients of variation (CV) from 14.1% to 27.3%, while FFP showed great inter-individual variation (CV 24.6% to 208.6%). Statistically significant differences were found across products (P ≤ 0.0095), and ABO blood groups (P = 0.0001). ConclusionAll three products can be used for the treatment of TTP. The choice of product depends on the need for additional viral safety, costs, product availability and the perceived impact of within-product variations.

Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura

AbstractThrombotic thrombocytopenic purpura (TTP), a potentially fatal blood clot disorder, is primarily caused by severe deficiency of plasma ADAMTS13 activity resulting from acquired autoantibodies. Plasma exchange is the only effective initial therapy. However, the high mortality rate and the complications associated with plasma exchange therapy remain a major concern. To address unmet clinical needs, therapeutic efficacies of anfibatide, a snake venom-derived platelet glycoprotein Ib antagonist, in murine models of spontaneous thrombocytopenia and shigatoxin-induced TTP were determined. A light scattering platelet aggregometry, microfluidic shear-based assay, and murine models of TTP were used in the study. We showed that purified anfibatide inhibits ristocetin- or botrocetin-induced human or murine platelet agglutination in the presence of von Willebrand factor in a concentration-dependent manner. Anfibatide could also dramatically inhibit the adhesion and aggregation of murine and human platelets on a collagen surface under arterial shear stress, in the presence or absence of plasma ADAMTS13 activity. Most importantly, we demonstrated that an intraperitoneal administration of anfibatide at the dose of 60 ng/g body weight twice daily mitigated spontaneous thrombocytopenia and prevented shigatoxin-induced TTP in Adamts13−/− and disease-susceptible mice (CAST/Ei strain). Thus, we conclude that anfibatide, when administered at the optimal dosage, route, and interval, is efficacious in treating spontaneous and bacterial shigatoxin-induced TTP in the murine models. Our findings may provide the basis for further development of anfibatide for the treatment of acute TTP in humans.

An Ischemic Stroke Related to Eltrombopag Use in a Patient with Idiopathic Thrombocytopenic Purpura

Thrombopoetin receptor agonists like eltrombopag, used for Idiopathic Thrombocytopenic Purpura treatment rarely cause to the ischemic cerebrovascular disease. In this report, a patient, have been followed by ITP diagnosis for 5 years, admitted to the emergency service for right hemiparesis and aphasia. It was diagnosed as ischemic cerebrovascular disease. Etiology of patient’s cerebrovascular event was associated with eltrombopag. Because of this rare seen situation, it was argued by in the light of the literature. Key words: Idiopathic thrombocytopenic purpura, thrombopoietin receptor agonist, eltrombopag, ischemic stroke

Purpura thrombopénique induit par la rifampicine chez une patiente non sensibilisée : à propos d’un cas

Thrombocytopenia induced by rifampicin in the absence of prior sensitization is exceptional, especially when it occurs in a patient without risk factors. We report the case of a patient aged 25 years with no past history of medical, surgical or knowledge of having taken rifampicin previously, who was hospitalized for treatment of thrombocytopenic purpura occurring after the initiation of fixed combination quadruple therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) for pulmonary tuberculosis. The biological pretreatment and therapeutic education had not been made. The patient presented with thrombocytopenic purpura 30000/mm(3) on day 9 after the initiation of treatment. The platelet count returned to normal 10 days after discontinuation of treatment. We elected not to reintroduce rifampicin given the strong likelihood that it was responsible for this complication. We conducted a phased reintroduction of isoniazid, ethambutol and pyrazinamide. No recurrence of the thrombocytopenia occurred. Thus, the diagnosis of rifampicin-induced thrombocytopenia appears to have been confirmed and the patient tolerated the remainder of their treatment well.

ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant: implications for selection of plasma preparations for thrombotic thrombocytopenic purpura treatment

Thrombotic thrombocytopenic purpura (TTP) is characterized by deficient ADAMTS13 activity. Treatment involves plasma exchange (PE). Both fresh-frozen plasma (FFP) and cryosupernatant (CSP) are used, but it remains to be determined which is more effective. To analyze the interaction between von Willebrand factor (VWF) and ADAMTS13, we used large-pore isoelectric focusing (IEF) analysis followed by detection with anti-ADAMTS13 monoclonal antibody. FFP, CSP, cryoprecipitate (CP), and purified ADAMTS13 were analyzed for their effects on high shear stress-induced platelet aggregation (H-SIPA). IEF analysis of normal plasma revealed three groups of ADAMTS13 bands with pI of 4.9 to 5.6, 5.8 to 6.7, and 7.0 or 7.5. Two band groups (pI 4.9-5.6 and 5.8-6.7) were found in plasma of a patient with Type 3 von Willebrand disease, in which VWF is absent, whereas no bands were found in plasma of a patient with congenital ADAMTS13 deficiency. Mixing these plasmas generated the bands at pI 7.0 or 7.5, representing the VWF-ADAMTS13 complex; these bands were absent in CSP. FFP and purified ADAMTS13 down regulated H-SIPA in a dose-dependent manner. However, CP did not inhibit H-SIPA in the initial phase, and the degree of inhibition at the endpoint was almost indistinguishable from those of the other two plasma products. Both plasma products (FFP and CSP) are effective for PE in TTP patients. However, CSP may be more favorable, because it has lower levels of VWF and almost normal ADAMTS13 activity, but lower levels of ADAMTS13 in complex with larger VWF multimers.

Is fresh‐frozen plasma clinically effective? An update of a systematic review of randomized controlled trials (CME)

BACKGROUND: The clinical use of frozen plasma (FP) continues to increase, both in prophylactic and in therapeutic settings. In 2004, a systematic review of all published randomized controlled trials (RCTs) revealed a lack of evidence that supported the efficacy of FP use. This is an update that includes all new RCTs published since the original review.STUDY DESIGN AND METHODS: Trials involving transfusion of FP up to July 2011 were identified from searches of MEDLINE, EMBASE, CINAHL, The Cochrane Library, and the UKBTS/SRI Transfusion Evidence Library. Methodologic quality was assessed. The primary outcome measure was the effect of FP on survival.RESULTS: Twenty‐one new trials were eligible for inclusion. These covered prophylactic and therapeutic FP use in liver disease, in cardiac surgery, for warfarin anticoagulation reversal, for thrombotic thrombocytopenic purpura treatment, for plasmapheresis, and in other settings, including burns, shock, and head injury. The largest number of recent RCTs were conducted in cardiac surgery; meta‐analysis showed no significant difference for FP use for the outcome of 24‐hours postoperative blood loss (weighted mean difference, −35.24 mL; 95% confidence interval, −84.16 to 13.68 mL). Overall, there was no significant benefit for FP use across all the clinical conditions. Only two of the 21 trials fulfilled all the criteria for quality assessment.CONCLUSION: Combined with the 2004 review, 80 RCTs have investigated FP with no consistent evidence of significant benefit for prophylactic and therapeutic use across a range of indications evaluated. There has been little improvement in the overall methodologic quality of RCTs conducted in the past few years.

Pregnancy-associated Thrombotic Thrombocytopenic Purpura: A Single Institution's Experience

AbstractAbstract 4675Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening form of microangiopathic hemolysis that can be associated with pregnancy. Although the association between TTP and pregnancy is well recognized, the presentation, natural history, and ideal treatment of TTP in this population remain poorly understood. St. Michael's Hospital is a regional referral centre for TTP in Ontario, Canada. We conducted a retrospective review of all cases of TTP referred to our pheresis unit between July 1993 and May 2010. Ninety-four cases were identified, of these, ten patients were pregnant or up to one week post-partum at the time of TTP diagnosis. Median age at presentation was 34 (29-36). Only one patient had been previously diagnosed with TTP and then developed a TTP relapse while pregnant. At presentation, all patients had thrombocytopenia (platelets: < 3 to 124 × 106/ml), anemia (hemoglobin: 60 to 99 mg/L), elevated LDH (1.3 to 12.5 × ULN), and fragmentation on blood film. ADAMTS13 was assessed in six of ten patients. It was normal in four patients, and deficient in two patients. Seven patients had neurological symptoms at presentation, one of whom suffered permanent right sided paralysis. Six patients had depressed glomerular filtration ratio (GFR) at presentation, four of these six recovered normal GFR. Hypertension was present in only one patient, and no patients had abnormal coagulation parameters at presentation. ALT was normal in six patients, mildly elevated in two patients, and unavailable in two patients. There were no patient deaths in this series. Patients were treated with a median of 17 plasma exchanges (range: 9 to 55) using either fresh frozen plasma or cryosupernatant. Eight patients achieved complete remission with plasma exchange. Two patients had refractory disease which ultimately responded to splenectomy and rituximab respectively. There were two fetal deaths, one a first trimester miscarriage, and the second an intrauterine death in the second trimester. In conclusion, in our series of pregnancy associated-TTP, there were no maternal deaths and most women responded to a short course of plasma exchange. ADAMTS13 deficiency was uncommon in our series. Nonetheless, in our series, TTP was not difficult to distinguish from preeclampsia and/or disseminated intravascular coagulation using routine laboratory parameters. Disclosures:No relevant conflicts of interest to declare.

Methylen Blue Photoinactivated Plasma vs Fresh Frozen Plasma in Thrombotic Thrombocytopenic Purpura Treatment: A Multicentric Prospective Cohort Study.

Plasma exchange (PE) with plasma infusion is the treatment of choice for Thrombotic Thrombocytopenic Purpura (TTP) but doubts remain as to whether all kinds of plasma are equally effective. Since October 2004, a multicentric prospective cohort study is being conducted in Spain to compare Methylene Blue Photoinactivated Plasma (MBPIP) with Fresh Frozen Plasma (FFP) in the treatment of TTP. Sixty-three first episodes of idiopathic TTP were included. MBPIP was used in 38 and FFP in 25. The treatment schedule consisted of daily PE (> 40 mL/kg of body weight) and costicosteroids (1.5 mg/kg/d). Response was defined as the achievement of a platelet count >= 150 x 109/L for at least three consecutive days, normal LDH level and absence of TTP-related symptoms and signs. Recurrence was defined as a fall in platelet count below 50 x 109/L or below 50% of the highest count achieved after response. Response lasting for more than 15 days was considered as remission. The prognostic significance of the kind of plasma used was investigated by logistic regression analysis after adjustment for other variables that had previously been found to influence on response to PE (gender; the Rock score; days from first medical attendance to PE; volume of plasma infused in the first 7 days of treatment). Both groups were comparable with regard to clinical and biological parameters at diagnosis. A severe deficit in ADAMTS13 activity was found in 9 out 12 (75%) patients treated with MBPIP and in 12 out of 16 (75%) patients treated with FFP. When compared to FFP, patients treated with MBPIP required a higher number of PEs (16±13 vs 9±7, p=0.004) and a larger volume of plasma (763±678 ml/kg vs 413±326 ml/kg, p=0.02) to achieve a remission and presented more recurrences while on PE treatment (21 out of 38 vs 6 out of 25, p=0.02). Splenectomy or rituximab was required in eight patients (21%) treated with MBPIP to achieve a remission vs in none out of the 25 patients treated with FFP (p= 0.02). After adjustment for other prognostic variables, patients in the MBPIP group had a lower likelihood of remission by the 8th treatment day (OR: 5.1; 95% CI: 1.6 – 15.9) and a higher risk of recurrence while on PE treatment (OR: 4.2; 95% CI: 1.3 – 13.5). In conclusion, MBPIP is less effective than FFP in the treatment of TTP.

Hematoma - Football

HISTORY: A 15 year-old high school linebacker sustained a direct blow to the right anterolateral shin during practice. The athlete had no apparent immediate injury and continued to practice. In the following hours, he developed a large bruise followed by swelling and dull pain in the right lower leg. There was no numbness, tingling, or weakness in the affected leg. The following day he was evaluated by his primary care physician. PHYSICAL EXAMINATION: Skin examination was remarkable for a 6cm x 8cm ecchymotic area (reddish-purple bruise) on the anterolateral aspect of the right shin. This area was minimally tender to palpation. There was also a fading bruise over the lower lumbar spine and numerous other small bruises in various stages of resolution on both arms and legs. There were no visible petechiae or purpura. There was no gingival bleeding or retinal hemorrhages. His abdomen was soft and nontender. The liver and spleen were not palpable. His extremity exam was significant for a left calf circumference of 36 cm, and a right calf circumference of 39.5 cm. His right calf was somewhat firmer than the left, but was not tender or tense. The distal extremities were well perfused. Range of motion and strength were normal. Sensation to light touch was intact and symmetrical. DIFFERENTIAL DIAGNOSIS: Traumatic hematoma Traumatic compartment syndrome Von Willebrand's disease Immune Thrombocytopenic Purpura Hemophilia TEST AND RESULTS: A CBC showed a white blood cell count of 11.1 with normal differential. His hemoglobin was 15.4 g/dl. The platelet count was markedly low at 10×103/ml (130–400× 103/ml). PT was slightly prolonged at 13.7 seconds (10–12 sec), INR was normal. Factor VIII, Von Willebrand Factor antigen, and VWF activity levels were all within normal limits. Antinuclear antibody (ANA) testing was negative. Bone marrow aspirate showed increased numbers of large, immature megakaryocytes, consistent with immune thrombocytopenic purpura. FINAL WORKING DIAGNOSIS: Immune (Idiopathic) Thrombocytopenic Purpura TREATMENT AND OUTCOMES: Oral steroids, high dose intravenous steroids, and intravenous immune globulin (IVIG) were minimally beneficial, and platelet counts remained low. Immunosuppressive therapy with 6-Merc apt op urine was successful in keeping platelets above 50×103/ml and was well tolerated by the patient. Weekly CBC's done the day prior to games. The athlete was allowed to participate in contact drills if weekly platelet count was greater than 50×103/ml. The athlete was prohibited from contact participation if platelet count was less than 50×103/ml and missed only one athletic contest as a result of low platelets.

Thrombotic Thrombocytopenic Purpura after Allogeneic Hematopoietic Stem Cell Transplantation: A Complication Still Frequent and Responsible of Severe Outcome.

IntroductionThrombotic thrombocytopenic purpura (TTP) might costitute a severe complication after hematopoietic stem cell transplantation (HSCT) with a variable incidence depending on different diagnostic criteria adopted in the past.Patients and MethodsThe current study enrolled 551 consecutive patients (pts) (314 males, median age 29 years) undergoing HSCT from January 2000 to April 2005 from HLA match (m) or mismatch (mm) family donor (350/551) and unrelated donor (201/551) for malignant (501/551) or non malignant diseases (50/551). The diagnosis of TTP was performed on the basis of homogeneous five clinical and seven laboratory criteria. Univariate (by chi square test and Fisher's exact test) or multivariate (by logistic regression method) analyses were performed to evaluate the effect of some candidate risk factors on both TTP occurrence and outcome.ResultsSixty four of 551 pts presented TTP (11,6%) at a median time of 47 days post-HSCT; 59/64 were affected by malignant and 5/64 by non malignant diseases. Multivariate analysis showed GVHD >II° (p=0,0001), stem cell donors (m/mm unrelated or mm related) (p=0,024), female gender (p=0,0186),TBI-based conditioning regimen (p=0,03) and status of hematological remission (p=0,03) as factors influencing the occurrence of TTP. Only three predicting factors for TTP outcome have been demonstrated statistically significative by multivariate analysis: age (p=0,0186), stem cell donors (m/mm unrelated or mm related) (p=0,01) and TTP index (p=0,018). The TTP mortality rate was 40% while the outcome after TTP diagnosis was partially influenced by TTP treatment. In particular, Defibrotide seemed to be a promising drug in univariate analysis compared with alternative therapies for 34 alive and good responders pts out of 64 TTP pts.ConclusionsThe study underlines the possibility to identify those patients who are more prone to develop post-HSCT TTP, complication still frequent (11,6%) when homogeneous diagnostic criteria are adopted. TTP outcome seems to be conditioned by some peculiar risk factors as adult age, m/mm unrelated or mm related donors HSCTs. Prospective randomized therapeutic trials, focusing on the possible advantage of Defibrotide versus other treatments, should be encouraged.

Recovery from idiopathic thrombocytopenic purpura (ITP) following right hemicolectomy for mucocele of appendix

A 61-year-old woman with a 2-year medication-free history of idiopathic thrombocytopenic purpura was referred to our hospital complaining of right lower abdominal pain. The platelet count was about 3-4x10(4)/mm3. This patient was diagnosed with mucocele of the appendix on computed tomography and colonoscopy. We performed only right hemicolectomy without splenectomy. The pathological diagnosis was mucinous cystadenoma of the appendix. The platelet count increased to 18.1x10(4)/mm3 on postoperative-day 7, and remained stable, at 20-24x10(4)/mm3, for 14 months after the operation. Platelet-associated immunoglobulin G decreased remarkably after the operation, to 30.2 ng/10(7) cells, from 240 ng/10(7) cells preoperatively. We describe the first case of recovery from idiopathic thrombocytopenic purpura following right hemicolectomy performed for mucocele of the appendix. Considering our patients clinical course, it is possible that mucinous cystadenoma of the appendix may have influenced the thrombocytopenia. Findings in this patient suggest that mucocele of the appendix may be associated with a new diagnosis and idiopathic thrombocytopenic purpura treatment.