Thrombotic Thrombocytopenic Purpura in a Patient with Sickle Cell Crisis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3963-3963
Author(s):  
Jumana S. Chatiwala ◽  
Gunwant Guron ◽  
Ibrahim Sidhom
Keyword(s):  
Platelet Count ◽  
Sickle Cell Disease ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Microangiopathic Hemolytic Anemia ◽  
Cell Disease ◽  
Thrombocytopenic Purpura ◽  
Sickle Cell Crisis

Abstract Thrombotic thrombocytopenic purpura (TTP) in association with sickle cell crisis is rare. We present a case of sickle cell crisis and TTP. This is 48 years old Nigerian male with history of mild sickle cell anemia since childhood presented with sickle cell crisis and mental state changes. On admission labs are hematocrit of 20 and platelet count of 212,000. He was treated for sickle cell crisis but developed acute dysuria and progressively worsening anemia (Hct-13.7) and thrombocytopenia (Plt-9000) with sickle cell and fragmented RBCs on peripheral smear with LDH of 8772. This picture was consistent with TTP. Patient was immediately started on plasma exchange. Patient received a course of plasma exchange as well as hemodialysis and his condition improved, with return of platelet count to normal (232), LDH to baseline (276). Patient was discharged with mild renal insufficiency (serum creatinine-2.3) off dialysis and plasma exchange. Conclusion: TTP is a micro vascular occlusive disorder characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. It is associated with pentard of signs and symptoms: thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on peripheral blood smear), neurological abnormalities, renal failure and fever. In practice thrombocytopenia, microangiopathic hemolytic anemia and elevated lactate dehydrogenase levels are often sufficient for the diagnosis. Our patient with sickle cell crisis was a diagnostic challenge and it is our belief that TTP evolved during inpatient therapy for painful crisis. We believe his hemolysis was due to sickle cell disease and TTP. The syndrome was reversed with prompt and aggressive treatment with plasmapharesis. (1, H. E. Lee, V. J. Marder, L. J. Logan, S. Friedman, B. J. Miller, Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease. Ann Hematol. 2003 Nov 82(11): 702–4. 2, Epub 2003 Aug 16. Chehal A, Taher A, Shamseddine A, Sicklemia with multi-organ failure syndrome and thrombotic thrombocytopenic purpura. Hemoglobin. 2002 Nov; 26(4): 345–51. 3, J. Bolanos-Meade, Y. K. Keung, C. Lopez-Arvizu, R. Florendo, E. Cobos, Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis. Ann Hematol. 1999 Dec 78(12): 558–9. 4, Geigel EJ, Francis CW, Reversal of multiorgan system dysfunction in sickle cell disease with plasma exchange. Acta Anaesthesiol Scand. 1997 May; 41(5): 647–50.)

scholarly journals Thrombotic Thrombocytopenia Purpura Case Series in Skmc 2016-2017

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4799-4799
Author(s):  
Mohamed Abu Haleeqa ◽  
Hanan Al Raeesi ◽  
Fatima Alkaabi
Keyword(s):  
Renal Failure ◽  
Mortality Rate ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Case Series ◽  
Therapeutic Plasma Exchange ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Patient Reported

Background and Purpose Thrombotic thrombocytopenic purpura (TTP) is a heterogeneous disease primarily characterized by thrombocytopenia and microangiopathic hemolytic anemia. Therapeutic plasma exchange has dramatically improved mortality, allowing for emergence of refractory, relapsing, and atypical presentations. in this case series we aim to present our institutional data for Apheresis in Sheikh khalifa medical City in AbuDhabi. We will also present patient demographic and clinical presentation and treatment protocol we use Methodology -Case series with Retrospective review. -Routine laboratory tests such as peripheral blood cell counts, reticulocyte count, coagulation profile, serum lactate dehydrogenase (LDH), bilirubin, serum creatinine, cardiac enzymes, and urinalysis, were performed. -ADAMTS13 levels and inhibitor titer were determined for all patient in outside lab -Baseline demographic characteristics were calculated in frequencies and percentages. (include age ,Gender , clinical manifestations and treatment strategy) Results and Discussions thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. less than 5 % of patient reported in literature have all associated clinical features. -Total of 10 patients M:F 4:2 , Median Age 44yr 50% presented with Neurological manifestations and renal disease , 30% presented with Fever only 20% had cardiac manifestation on admission . None of the patient presented with all 5 pentad. -All patients received TPE , steroid . -90 % of the patients received Rituximab except for 1 because of Allergy. -All patients has low ADAMTS 13 , except one has normal ADAMTS13 but came with relapse and on first admission had low ADAMTS13 -All patient presented with MAHA and TCP except 2 patient whom had normal Hb but significant schistocytes on peripheral blood with TCP both patient where relapsed cases. -3 patient were relapsed 7 de novo , the 3 relapsed cases all did not receive Rituximab in first remission . One of them relapsed twice but did not received Rituximab due to allergy -Although some publication include large number of TTP patients, but only few case reports have evaluated the clinical feature, laboratory parameters and therapeutic outcome of TTP. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. A disintegrin and metalloprotease with thrombospondin Type 1 motif, Member 13 (ADAMTS13) levels less than 5% are a hallmark of TTP. We do ADAMTS 13 Activity and inhibitor titre levels in outside facility TAWAM hospital with turn-around time of 7 days which is helpful in planning Rituximab treatment. with availability of Rituximab our relapse rates are low but not zero Conclusions -Thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. -5 % of patient reported in literature have all associated clinical features. -We found that majority of patient presented with evidence of thrombocytopenia and MAHA only. -Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. -TPE ,steroid and rituximab was very effective in achieving sustain remission in 100% of ours patients with median follow up 8 month -More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Thrombotic Thrombocytopenic Purpura: A Case Series from a Tertiary Care Centre in Northern India

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5006-5006
Author(s):  
Sanjeev Kumar Sharma ◽  
Dharma Choudhary ◽  
Meet P. Kumar ◽  
Rasika Setia ◽  
Vipin Khandelwal ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Case Series ◽  
High Index ◽  
Medical Emergency ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Post Transplant ◽  
High Index Of Suspicion

Abstract Abstract: Thrombotic thrombocytopenic purpura is a medical emergency with varied clinical manifestations. High index of suspicion with careful evaluation of thrombocytopenia and hemolytic anemia is of paramount importance. Laboratory parameters of microangiopathic hemolytic anemia i.e. schitocytosis and increased LDH and indirect hyperbilirubinemia support the diagnosis. Plasma exchange is the treatment of choice. Post stem cell transplant TTP carries a poorer prognosis. Introduction: Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia associated with fever, renal dysfunction and neurological manifestations. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange mortality decreases to about less than 10% (1). Recent reports indicate that rituximab can induce remission in the majority of patients with classic TTP (2). We report here 13 cases of TTP who were treated at our hospital in last 4 years. Six of these patients developed features of TTP post allogenic stem cell transplantation. Materials and Methods: The study included retrospective analysis of patients who presented with the features of TTP. Patients with characteristic features of TTP included two or more features among the pentad commonly considered diagnostic of TTP. Evidence of microangiopathic hemolytic anemia and thrombocytopenia were the minimal requirement for the diagnosis with or without fever, renal dysfunction and neurological manifestations. Coagulation profile included prothrombin time and APTT. Liver and kidney function analysis was done in all patients. Response was assessed by clinical and laboratory parameters with monitoring platelet counts, LDH, and schistocytes in the peripheral blood film. Patients with LDH in normal range and platelet counts more than 100,000/µl were considered to have achieved remission. Results: Patients with classic TTP recovered with plasma exchange and/or rituximab. Post-transplant TTP patients had a poorer prognosis as five out of six post-transplant TTP patients died. Discussion: TTP can have a varied clinical presentation and can be associated with many other diseases. Our case series highlight the varied manifestations and associations of TTP and their management and outcome. TTP is a medical emergency and needs high index of suspicion for the diagnosis. In our series, TTP was diagnosed by the findings of thrombocytopenia and hemolytic anemia evidenced by presence of schistocytes in the peripheral blood film and increased LDH, in the absence of coagulopathy. TTP should be suspected in the presence of microangiopathic hemolytic anemia and thrombocytopenia (1,3), and treatment should be started immediately, as delay in treatment can increase the mortality (1). Plasma exchange has changed the prognosis of this highly fatal disease to a highly curable disease. Rituximab has further improved the management of TTP (2). Patients with classic TTP were treated with plasma exchange but 3 patients also required rituximab. All patients with classic TTP are in remission. Transplant-associated microangiopathy (TAM) is a MAHA and thrombocytopenia that occurs after bone marrow transplantation. Patients with post-transplant TTP were diagnosed based on thrombocytopenia and features of microangiopathic hemolytic anemia with schistocytosis and raised LDH, in the absence of coagulopathy. They were treated with FFP and steroids, as plasma exchange is not beneficial for post-transplant TTP (1). Repeated plasma exchange with increased frequency and/or rituximab therapy are the agents of choice in relapsing disease (3). Rituximab is a safe and effective treatment for newly diagnosed TTP, and has been shown to decrease the number of plasma exchange required to achieve remission. We used rituximab in 3 patients and all improved. Post transplant MAHA carried poor prognosis. Conclusion: Diagnosis of TTP requires a high index of suspicion and prompt treatment with plasma exchange, which results in a high cure rate. Rituximab is useful in patients relapsing or showing partial recovery. Plasma exchange has not been reported to be effective in post-transplant TTP. Acknowledgment: We are thankful to Ms Bharti Sharma for compiling the data. Disclosures No relevant conflicts of interest to declare.

scholarly journals Concurrent Bilateral Central Retinal Artery Occlusion Secondary to Sickle Cell Crisis

2021 ◽  
Vol 9 ◽  
pp. 232470962110283
Author(s):  
Gowri Renganathan ◽  
Piruthiviraj Natarajan ◽  
Lela Ruck ◽  
Roberto Prieto ◽  
Bharat Ved Prakash ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vision Loss ◽  
Central Retinal Artery Occlusion ◽  
Retinal Artery Occlusion ◽  
Artery Occlusion ◽  
Cell Disease ◽  
Sickle Cell Crisis ◽  
History Of ◽  
Retinal Artery

Vascular occlusive crisis with a concurrent vision loss on both eyes is one of the most devastating disability for sickle cell disease patients. Reportedly occlusive crisis in the eyes is usually temporary whereas if not appropriately managed can result in permanent vision loss. A carefully managed sickle cell crisis could prevent multiple disabilities including blindness and stroke. We report a case of a 24-year-old female with a history of sickle cell disease who had acute bilateral vision loss during a sickle crisis and recovered significantly with a timely emergent erythrocytapheresis.

Plasma exchange in critically ill patients with sickle cell disease

2007 ◽  
Vol 37 (1) ◽  
pp. 17-22 ◽  
Author(s):  
C. Boga ◽  
I. Kozanoglu ◽  
H. Ozdogu ◽  
Emel Ozyurek
Keyword(s):  
Sickle Cell Disease ◽  
Plasma Exchange ◽  
Critically Ill ◽  
Sickle Cell ◽  
Critically Ill Patients ◽  
Cell Disease

scholarly journals Sickle Cell Disease Model Mice Lacking 2,3-Dpg Show Reduced RBC Sickling and Improvements in Markers of Hemolytic Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Kelly M. Knee ◽  
Amey Barakat ◽  
Lindsay Tomlinson ◽  
Lila Ramaiah ◽  
Zane Wenzel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Organ Damage ◽  
Complete Elimination ◽  
Cell Disease ◽  
The Impact ◽  
2,3 Dpg

Sickle cell disease (SCD) is a severe genetic disorder caused by a mutation in hemoglobin (b6Glu-Val), which allows the mutant hemoglobin to assemble into long polymers when deoxygenated. Over time, these polymers build up and deform red blood cells, leading to hemolytic anemia, vaso-occlusion, and end organ damage. A number of recent therapies for SCD have focused on modulating the mutant hemoglobin directly, however, reduction or elimination of 2,3-DPG to reduce Hb S polymerization and RBC sickling has recently been proposed as a therapeutic strategy for SCD. Current clinical studies focus on activation of pyruvate kinase to reduce 2,3-DPG, however, direct targeting of the enzyme which produces 2,3-DPG; Bisphosphoglycerate Mutase (BPGM) may also be possible. In this study we evaluate the impact of elimination of 2,3-DPG on SCD pathology by complete knockout of BPGM in Townes model mice. Animals with complete knockout of BPGM (BPGM -/-) have no detectable 2,3-DPG, while animals that are heterozygous for BPGM (BPGM -/+) have 2,3-DPG levels comparable to Townes mice. Western Blot analysis confirms that BPGM -/- animals completely lack BPGM, while BPGM -/+ animals have BPGM levels that are nearly equivalent to Townes mice. As expected from the lack of 2,3-DPG, BPGM -/- animals have increased oxygen affinity, observed as a 39% decrease in p50 relative to Townes mice. Complete elimination of 2,3-DPG has significant effects on markers of hemolytic anemia in BPGM -/- mice. Mice lacking 2,3-DPG have a 60% increase in hemoglobin (3.7 g/dL), a 53% increase in red blood cell count, and a 29% increase in hematocrit relative to Townes mice. The BPGM -/- mice also have a 57% decrease in reticulocytes, and a 61% decrease in spleen weight relative to Townes animals, consistent with decreased extramedullary hematopoiesis. Consistent with the reduction in hemolysis, BPGM -/- animals had a 59% reduction in red blood cell sickling under robust hypoxic conditions. BPGM -/+ animals had hemoglobin, RBC, and hematocrit levels that were similar to Townes animals, and a similar degree of RBC sickling to Townes mice. Liver phenotype was similar across all variants, with areas of random necrosis observed in BPGM -/-, BPGM -/+ and Townes mice. Higher percentages of microcytic and/or hyperchromic RBCs were observed in BPGM -/- animals relative to BPGM -/+ or Townes animals. These results suggest that modulation of 2,3-DPG has a positive effect on RBC sickling and hemolytic anemia, which may have therapeutic benefits for SCD patients. However, the lack of improvement in organ damage suggests that modulation of 2,3-DPG alone may not be sufficient for complete elimination of SCD phenotypes, and further investigation of this therapeutic avenue may be necessary. Disclosures No relevant conflicts of interest to declare.

Sickle cell crisis as evaluated from measurements of hydroxybutyrate dehydrogenase and myoglobin in plasma.

1981 ◽  
Vol 27 (2) ◽  
pp. 314-316 ◽  
Author(s):  
E F Roth ◽  
P A Bardfeld ◽  
S J Goldsmith ◽  
E Radel ◽  
J C Williams
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
High Specificity ◽  
Mean Value ◽  
Cell Disease ◽  
Sickle Cell Crisis ◽  
The Mean ◽  
Low Sensitivity ◽  
Sickle Cell Crises

Abstract Data on plasma hydroxybutyrate dehydrogenase activity (I) and myoglobin concentration were used to evaluate painful sickle cell crises. I was increased during non-crisis steady state in patients with sickle cell disease as compared to normal values (232, SD 79.7 vs 85, SD 33 Sigma units/mL). During crisis, the mean value for I increased further to 379 (SD 139) Sigma units/mL. For 12 patients evaluated both during steady state and crisis, there was a mean increase in plasma I of 131% (SD 76%). Repeated determinations of I in sickle cell disease patients during several months while they were in steady state showed that baseline I varied by no more than 20% from the mean. Plasma myoglobin in patients with sickle cell disease was not above normal, but during crisis 21 of 39 patients tested had increased plasma myoglobin concentrations. Our data suggest that I may be a useful indicator of sickle cell crisis when the patient's own baseline value is available for comparison. Plasma myoglobin measurements give evidence of muscle damage during crisis with high specificity but low sensitivity.

scholarly journals 3458 Temporal Trends and Outcomes of Opioid Abuse among Adolescents & Young Adult Sickle Cell Disease Patients

2019 ◽  
Vol 3 (s1) ◽  
pp. 54-55
Author(s):  
Nnaemeka E Onyeakusi ◽  
Adebamike Oshunbade ◽  
Fahad Mukhtar ◽  
Adeyinka Adejumo ◽  
Semiu Gbadamosi ◽  
...  
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Temporal Trends ◽  
Opioid Abuse ◽  
P Value ◽  
Total Charge ◽  
Inpatient Mortality ◽  
Cell Disease ◽  
Sickle Cell Crisis

OBJECTIVES/SPECIFIC AIMS: In this study, we aim to describe temporal trends in opioid abuse among adolescents and 11-21years and young adults 22-35years with Sickle cell disease hospitalized for sickle cell crisis. We also aim to evaluate clinical and healthcare utilization outcomes of opioid abuse in the same population. In addition, we hope to assess for difference in effect by age category. METHODS/STUDY POPULATION: Our study is a cross-sectional study of data secondarily sourced from the 2007-2014 National Inpatient Sample(NIS), a component of the Healthcare Utilization Project (HCUP). Variables were identified using ICD-9-CM codes. We selected inpatient stays for patients aged 11-35 years admitted for sickle cell crisis. Opioid abuse was the primary outcome of interest. Secondary outcomes were inpatient mortality, total charge, length of stay and select clinical outcomes. We analyzed our data for trends and outcomes. We performed trend analysis of prevalence rates between 2007-2014 by age categories. Propensity-Matched Score regression models were deployed to assess for associations between opioid abuse and outcomes while adjusting for relevant covariates. Sub-group analysis of opioid abuse by age was assessed for outcomes of interest. Trend analysis was performed on Joinpoint Software v4.6.0, (National Cancer Institute, NIH, Bethesda, MD). Outcome analysis was performed on SAS v9.4 (SAS Institute, Cary, NC). Statistical significance was set at 95% and p-value of 0.05, two-tailed. RESULTS/ANTICIPATED RESULTS: Of 86,827 inpatients admitted for sickle cell crisis, 2,363 (2.73%) had a diagnosis of opioid abuse while 84,464 (97.27%)did not abuse opioids. 27,004 (31.01%) of admitted patients were 11-21 years while 59,823 (68.99%) were 21-35 years. We found statistically significant APCs (Annual Percentage Change) showing increasing trends in both age categories for years under review, (18.47% [95% CI 15.39-21.63]; p-value <0.001 in young adults vs. 10.31% [95% CI 3.58-17.49]; p-value 0.009 in adolescents). The difference in APCs between both age categories were also significant (−8.16% [95% CI [−14.26-2.05]; p-value 0.009). There were no parallelism or coincidence in the trend lines. Opioid abuse was found to be associated with significantly longer length of stay (7.74 vs 6.05 days), higher total charge ($40,797 vs $32,164), (aOR 1.44; 95% CI [1.19-1.75]) seizures, sepsis (aOR 1.62; 95% CI [1.35-1.94]) and pulmonary hypertension (aOR 1.36; 95% CI [1.12-1.66]). No significant association was found for inpatient mortality, transfusion, cardiac dysrhythmias, pulmonary embolism and acute kidney injury. Significant interaction existed between opioid abuse and age for total charge (for $41,869 vs $29,371 among adolescents & $40,632 vs $32,550 among young adults; interaction p-value 0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Trends show a significant increase in the prevalence of opioid abuse among adolescents and an increasingly higher prevalence when adolescents transition to young adults. Opioid abuse among sickle cell patients is associated with significant poor healthcare resource utilization and clinical outcomes. Public health interventions to prevent worsening opioid abuse prevalence are expected to improve patient outcomes.

Severity of Sickle Cell Disease: Modeling Interrelationships among Hemolysis, Pulmonary Hypertension and Risk of Death.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 786-786
Author(s):  
Paola Sebastiani ◽  
Vikki G. Nolan ◽  
Clinton T. Baldwin ◽  
Maria M. Abad-Grau ◽  
Ling Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Disease Severity ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Risk Of Death

Abstract A single point mutation in the β hemoglobin gene causes sickle cell disease (SCD), but patients have extremely variable phenotypes. Hemolysis-related complications include pulmonary hypertension (PHT), priapism, stroke and leg ulceration; blood viscosity and sickle vasoocclusion are associated with painful episodes, acute chest syndrome and osteonecrosis. Predicting who is at highest risk of death would be useful therapeutically and prognostically. Applying Bayesian network modeling that describes complex interactions among many variables by factorizing their joint probability distribution into modules, to data from 3380 SCD patients, we constructed a disease severity score (DSS: 0, least severe; 1, most severe), defining severity as risk of death within 5 years. A network of 24 variables described complex associations among clinical and laboratory complications of SCD. The analysis was validated in 140 patients whose SCD severity was assessed by expert clinicians and 210 adults where severity was also assessed by the echocardiographic diagnosis of PHT and death. Information about PHT allowed a comparison of the DSS with the tricuspid regurgitant jet velocity (TRJV), an objective marker of PHT and an independent risk factor for death. DSS and three indices of clinical severity (severity ranking of individuals by expert clinicians; objective measurement of the presence and severity of PHT; risk of prospective death) were correlated. Among living subjects, the median score was 0.57 in 135 patients without PHT, 0.64 in 40 patients with mild PHT and 0.86 in 15 patients with severe PHT. The difference in average score between living patients with and without PHT is significant. The same increasing trend was noticeable in the subjects who died during follow-up: 0.60 in subjects without PHT; 0.68 in subjects with mild PHT; 0.79 in subjects with severe PHT. The utility of the DSS is also supported by the ability to assign a score to subjects for whom the TRJV cannot be measured. Surprisingly, besides known risk factors like renal insufficiency and leukocytosis, we identified the intensity of hemolytic anemia and clinical events associated with hemolytic anemia as contributing to risk for death. Priapism, an excellent reflection of the hemolytic anemia-related complications of SCD, is associated with PHT and its association with death was unexpected. Laboratory variables predictive of disease severity included LDH and reticulocytes that reflect the intensity of hemolytic anemia. Elevated systolic blood pressure increased the odds of death by 3.4, consistent with hypertension as a marker of early death in SCD. Subjects with sickle cell anemia are at greatest risk compared with subjects with sickle cell anemia-α thalassemia and with subjects with HbSC disease. Our model suggests that the intensity of hemolytic anemia, estimated by LDH, reticulocyte count and AST, and shown previously to be associated with PHT, priapism, leg ulceration and possibly stroke, is an important contributor to death. This model can be used to compute a personalized measure of disease severity that might be useful for guiding therapeutic decisions and designing clinical trials.

Safety and Efficacy of Mycophenolate Mofetil in Relapsing Acquired Thrombotic Thrombocytopenic Purpura: Could It Prevent Further Relapse?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3993-3993 ◽  
Author(s):  
Sameer A. Tulpule ◽  
Yvonne A. Francis ◽  
Deepti Radia ◽  
Claire N. Harrison ◽  
Beverely J. Hunt
Keyword(s):  
Platelet Count ◽  
Mycophenolate Mofetil ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Maximum Dose ◽  
Case Series ◽  
Initial Presentation ◽  
Thrombocytopenic Purpura ◽  
Methyl Prednisolone ◽  
Threatening Condition

Abstract Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life threatening condition requiring rapid diagnosis and treatment. Plasma exchange (PEX) is the mainstay of treatment. Various forms of immunosuppression (IS) have been used which include steroids, cyclosporine, cyclophosphamide, vincristine and rituximab. The percentage of patients relapsing is unclear. There is a suggestion that up to half of the patients with severe acquired deficiency of von Willebrand factor -cleaving protease (vWF-CP) activity relapse within a year. There are no reports of the use of mycophenolate mofetil (MMF) in acquired TTP. We describe three patients with acquired TTP, treated with MMF at relapse, with the intention to prevent further relapse. Methods: The 3 patients presented with acute acquired TTP. They all had at least 3 of the clinical pentad of fever, microangiopathic haemolytic anaemia, thrombocytopenia, neurological and renal impairment plus a vWF-CP level of &lt; 2% at initial presentation. All of them underwent PEX until remission (platelet count of &gt;150 x 109/L for at least 2 consecutive days with resolution of neurological and renal signs). MMF was introduced at remission after relapse at a dose of 500mg BD, post PEX, increasing upto a maximum dose of 750 mg BD. MMF was introduced at 4th relapse for patient A, 2nd relapse for patient B and 1st relapse for patient C. Results: All 3 patients were females. The ages at presentation were 63, 72 and 46 years. At presentation, the haemoglobin was 6.0, 8.7 and 6.7 g/dL and platelet count was 19, 36 and 21 x 109 /L respectively. Patient A relapsed eight times at day (d) 9, d20, d53, d89, d198, d209, d221 and d231. She was treated with PEX in conjunction with steroids and vincristine, cyclosporine, cyclophosphamide and rituximab for the first 3 relapses respectively. During the third relapse the patient’s condition deteriorated and she became unconcious requiring ventilation. MRI brain showed multiple small foci consistent with vascular disease. She recovered, but relapsed again despite cyclophosphamide and rituximab. After the 4th relapse on d102, MMF was started reaching a maximum dose of 750mg BD. She had regular full blood counts checked. At d187 she was found to be neutropenic and the MMF was stopped. She relapsed in 11 days and was recommenced on MMF at 500mg bd after PEX. MMF was continued at the dose of 750mg BD after the 7th and 8th relapse. Despite full dose MMF, she relapsed and was treated with PEX and a further course of rituximab was given at the 8th relapse. Patient B had received 500mg of methyl prednisolone on ITU with PEX at initial presentation. MMF (500mg BD) was commenced at remission after second relapse (d23) after undergoing plasma exchange. Patient C was commenced on MMF (500mg BD) after first relapse (d36). All 3 are in remission and continue on MMF at a follow up of 12, 2 and 4 months respectively since last relapse. MMF was tolerated very well except for transient neutropenia (patient A) and transient diarrhoea (patient C). Conclusion: MMF appears to be safe in patients with relapsed TTP who received multiple lines of treatment. Due to the small size of this case series it is unclear whether MMF is efficacious in reducing the risk of relapse in TTP; a formal longer study may be warranted.

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