Disseminated Malignancy Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Report of 10 Patients and a Systematic Review of Published Cases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1062-1062
Author(s):  
Kristin K. Francis ◽  
Nalini Kalyanam ◽  
Deirdra R. Terrell ◽  
Sara K. Vesely ◽  
James N. George
Keyword(s):  
Systematic Review ◽  
Bone Marrow ◽  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Bone Marrow Biopsy ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
History Of Cancer ◽  
Systemic Malignancy

Abstract Patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura (TTP), resulting in inappropriate plasma exchange treatment, a procedure with major risk, and delay of appropriate chemotherapy. We report the 17 year experience of The Oklahoma TTP-HUS Registry, 1989–2005, and a systematic review of previously published case reports. Ten of 335 consecutive patients in the Oklahoma Registry who were initially diagnosed with their first episode TTP and treated with plasma exchange were subsequently discovered to have disseminated malignancy; only one had a history of cancer. These 10 patients were compared to the 133 concurrent patients with idiopathic TTP. Disseminated malignancy (n=10) Idiopathic TTP (n=133) P Data are median values. P-value for neurologic symptoms compares distribution of abnormalities. Number of patients who had ADAMTS13 measured is in parentheses. 8 idiopathic TTP patients never had plasma exchange (PE). Age (years) 56 47 0.106 Sex (% female) 30% 73% 0.008 Duration of sx (days) 21 8 0.005 Presenting sx Weakness 70% 53% 0.347 cough, dyspnea 70% 26% 0.007 Fever 50% 31% 0.292 abdominal pain 40% 35% 0.745 Nausea/vomiting 20% 53% 0.052 Neurologic abnormalities Severe 20% 47% 0.128 Minor 60% 29% None 20% 24% Laboratory data hematocrit (%) 21 22 0.868 platelet count (103/ml) 21,000 13,000 0.328 creatinine (mg/dL) 2.4 2.0 0.761 LDH (U/L) 2894 1260 0.045 ADAMTS13 Median activity (%) 50(8) 23 (81) 0.167 <5% activity (% of pts) 0 30% 0.102 Response to PE 10% 82% (125) <0.001 Death (within 30 days) 90% 20% <0.001 Patients with disseminated malignancy had a longer duration of symptoms, were more often men, had more frequent presence of respiratory symptoms, higher LDH levels, more often failed to respond to plasma exchange treatment, and had a higher mortality. Neurologic abnormalities, hematocrit, platelet count, and serum creatinine were not different between the two groups. Diagnosis of malignancy was made by bone marrow biopsy in 6 patients but not until autopsy in 2 patients. A systematic review identified 19 additional patients, reported from 1965 to 2005, in whom TTP or HUS was initially suspected and systemic malignancy subsequently discovered. Only 5 patients had a history of cancer. Malignancy was not diagnosed until autopsy in 6 patients. Fourteen different malignant disorders were diagnosed in these 29 patients. CONCLUSIONS: Disseminated malignancy may be occult and may mimic TTP. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients diagnosed with TTP have atypical clinical features or fail to respond to plasma exchange.

TTP, ET, and ITP Sequential Occurrence in a Single Patient: a Case Report

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4573-4573
Author(s):  
Mirna H Farhat ◽  
Amr Hanbali
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Case Report ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Bone Marrow Biopsy ◽  
Essential Thrombocythemia ◽  
Lupus Erythematosus ◽  
Treatment Modalities ◽  
Peripheral Smear ◽  
Thrombocytopenic Purpura

Abstract INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP), essential thrombocythemia (ET) and idiopathic thrombocytopenic purpura (ITP) are three separate disease entities that affect the platelets. Each has a different pathophysiology clinical presentation and consequences. We present a case where TTP, ET, and ITP were diagnosed in the same patient at different times of her clinical course with the aim of drawing the attention to this undocumented occurrence which remains under investigation. CASE REPORT: A 42 year old African American female was diagnosed in 1994 with TTP after she presented with slurring of speech and left upper extremity weakness. Her hemoglobin was 9.7 g/dL, creatinine of 1.3 mg/dL, LDH of 448 IU/L and her peripheral smear showed schistocytes. She was diagnosed with TTP and was treated with plasma exchange with improvement in the platelet count. In March 2001, she presented with purple toe syndrome and a platelet count of 877,000. Bone marrow biopsy revealed panmyeloid hyperplasia, clustering of megakaryocytes, and stainable iron. She was then diagnosed to have essential thrombocythemia and was started on Anagrelide, which was later switched to Hydroxyurea. In October 2001, Hydroxurea was stopped and two weeks later, her platelet count dropped to 12,000. Investigations including a bone marrow biopsy were done which showed megakaryocytes in atypical clusters. No schisocytes were seen on peripheral smear. The patient’s platelet count dropped to 7,000 and she was transfused with 12 units of platelets. Post transfusion her count was 90,000 but dropped to 25,000 in less than 12 hours. She was then started on IV immunoglobulins and steroids for a presumptive diagnosis of ITP and her platelet count subsequently improved. Subsequent outpatient evaluation was negative for ANA, C3, C4, and HIV CONCLUSION: The fact that both immune and thrombotic thrombocytopenic purpura occur with increased frequency among persons with systemic lupus erythematosus, HIV disease, or pregnancy supports the hypothesis that some pathophysiologic factors are shared. As the three conditions have different natural histories and require different treatment modalities, it is important to recognize that these diseases may be seen sequentially and here comes the importance of reviewing peripheral blood smears for evaluation of thrombocytopenia and bone marrow aspirations for diagnosis of thrombocythemia in order to reach an accurate diagnosis and tailor therapy accordingly. This case demonstrates the variability and complexity of platelet disorders. Platelets may go one way or another and can even go in opposite directions in the same person. After reviewing the literature, there are no reported cases of TTP, ET, and ITP diagnosed in the same patient. Our aim is to draw the attention to this rare case which is still under investigation.

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 < 2% at initial presentation. All of them underwent PEX until remission (platelet count of >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.

scholarly journals Rituximab for Prevention of Recurrent Pregnancy Related Thrombotic Thrombocytopenic Purpura in High Risk Patients with Previous Episodes of Thrombotic Thrombocytopenic Purpura during Pregnancy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4940-4940 ◽  
Author(s):  
Anusiyanthan Isaac Mariampillai ◽  
Michael Garrison ◽  
Alice A. Zervoudakis
Keyword(s):  
High Risk ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Post Partum ◽  
Blood Chemistry ◽  
Peripheral Smear ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
Suspected Recurrence ◽  
Risk Of Relapse

Abstract Introduction We describe the use of rituximab for the successful prophylaxis and delivery of a multiparous female with a history of pregnancy related thrombotic thrombocytopenic purpura (TTP) now presenting with a high risk of relapse during subsequent pregnancy. Case Presentation A 33 year-old African American female with a history of post-partum TTP diagnosed two years prior was referred to the hematology clinic for suspected recurrence of her TTP at 22 weeks gestation. Two years ago the patient had presented with symptoms of severe headache and hypertension which began 1 week after the delivery of her 3rd child. She was referred to the emergency department where she was found to have microangiopathic hemolytic anemia with a hemoglobin of 7.6g/dL, platelets of 10k/uL and abundant schistocytes on peripheral smear. Her blood chemistry revealed renal failure with an elevated creatinine of 2.7mg/dL, LDH of 2001 IU/L. She was found to have a moderately low ADAMTS13 level of 16% (normal >66%) and an inhibitor was detected (1.0 BEU). Her ANA, HIV, hepatitis and lupus serologies were all negative. Her C3 level was 105 (normal 70-225mg/dL) and C4 was 20 mg/dL (normal 14-55 mg/dL). She was promptly initiated on plasma exchange in addition to magnesium supplementation and strict blood pressure control. She underwent 11 days of daily plasma exchange and steroids with improvement of her platelets and resolution of schistocytes on peripheral smear. Despite this, she again had rise in her parameters and rituximab was added to the regimen which she responded to with continued normalization of her hematologic parameters and clinical resolution of symptoms. Approximately 2 years later, the patient presented again at 22 weeks gestation of her fourth pregnancy for suspected recurrence of her TTP. Blood chemistry revealed a low ADAMTS13 (<3%), anemia (Hb 10.8g/dL) and moderate thrombocytopenia (platelets 156k/uL). Her liver and renal functions were unaffected and she had no evidence of bruising or bleeding on physical exam. Serial repeat testing showed persistently low ADAMTS13 level (<3%) and worsening thrombocytopenia (platelets decreased to 113k/uL) without development of other clinical manifestation of TTP. Prophylactic plasma exchange was offered to the patient however the patient declined due to its associated risks. She was initiated on weekly rituximab (375mg/m2) with decadron (6mg weekly) from 27th to 30th weeks of pregnancy. After 4 infusions, her platelets improved to 190k/uL along with an increase in ADAMTS13 level to 62%. A healthy male child weighing 3.2 kilograms was delivered by C-section at 36 weeks without complications. Post-partum, the patient's CBC remained stable with platelets above 100k/dL along with her LDH, haptoglobin and renal function and was subsequently discharged with no further documentation of relapse in her TTP. Discussion TTP is a severe, and often life threatening condition characterized clinically by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, neurologic changes and fever. Pregnancy is a known trigger for onset of TTP and has been well described in literature, usually presenting in the third trimester or post-partum period with a constellation of symptoms that may mimic other thrombotic microangiopathies (Martin JN Jr, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol.2008; 199(2):98-104). Recurrent TTP complicating subsequent TTP is uncommon (George. JN, et al.Blood, 2014; 123 (11):1674-1680). Patients with a history of pregnancy related TTP continue to be at high risk of relapse with subsequent pregnancies and their management often presents as a challenge to both hematologist as well as obstetricians . While plasma exchange and immunosuppression is a cornerstone of successful treatment of confirmed pregnancy related TTP, literature regarding optimal prophylaxis to prevent the onset of subsequent TTP in women with a history of pregnancy related TTP is lacking. Rituximab for the prevention of TTP relapse during pregnancy may be a viable option. Disclosures No relevant conflicts of interest to declare.

scholarly journals Thrombotic thrombocytopenic purpura and dose of plasma exchange

Blood ◽  
1979 ◽  
Vol 54 (4) ◽  
pp. 842-849 ◽  
Author(s):  
EG Taft
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Exchange Transfusion ◽  
Residual Disease ◽  
Blue Dye ◽  
Success Rates ◽  
Thrombocytopenic Purpura ◽  
Adequate Dose ◽  
Ldh Activity

Abstract Four patients with thrombotic thrombocytopenic purpura (TTP) were treated by plasma-exchange transfusion, three of whom recovered completely. Because previous reports in the literature describing exchange transfusion as treatment for TTP have demonstrated variable success rates, particular attention was given to “dose”and frequency of plasma exchange. Evans blue dye studies established a measure of “dose” under conditions of varying efficiency. Serum LDH activity was found to be diminished by plasma exchange, and the rate of return of serum LDH activity reflected residual disease activity. The magnitude of LDH activity reduction correlated with the adequacy of dose of plasma exchange and was an indicator for the need of repeated daily exchanges. Failure to obtain a spontaneous increment in platelet count also suggested the need for additional exchanges and/or larger dose of exchange. There is a need for a standard expression of dose of plasma exchange. Utilizing these markers (LDH, platelet count), it may be possible to improve the survival in TTP if adequate dose and frequency of plasma exchange are used.

Pregnancy Associated Thrombotic Thrombocytopenic Purpura: A Case Report.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3221-3221
Author(s):  
Xu Ye ◽  
Ying Feng ◽  
Ying Pang ◽  
Zhaoyue Wang
Keyword(s):  
Bone Marrow ◽  
Renal Function ◽  
Platelet Count ◽  
Case Report ◽  
Partial Response ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Oral Prednisolone ◽  
Thrombocytopenic Purpura ◽  
Blood Routine

Abstract Introduction: In clinical setting, cases with thrombotic thrombocytopenic purpura (TTP) are easily mis-diagnosed and the clinical outcome may be influenced by the mis-diagnosis. Case report: The patient is a 28-year-old woman in her first pregnancy. She had transient thrombocytopenia two years ago and was diagnosed idiopathic thrombocytopenic purpura (ITP) based on her bone marrow results but recovered quickly without immunosuppressive therapy. Her blood routine test was normal before the pregnancy. But she was found to have asymptomatic thrombocytopenia during her first pregnancy check-up in the first trimester of her pregnancy. A diagnosis of ITP was made after bone marrow examination. Then, she was put on a course of oral prednisolone and her platelet count transiently increased to normal but decreased to 18×109/L after she cut down on the dose. After that, she only showed partial response to increased dose of oral prednisolone and her hemoglobin (Hb) level began to fall slowly. She was admitted during her second trimester of gestation complaining of headache and low fever with signs of agitation. Blood routine, blood smear analysis, urine routine, liver function and blood bilirubin analysis, renal function tests were performed regularly. Bone marrow smear examination, tests for detecting various causes of hemolysis and tests detecting autoimmune antibodies were also performed. Her lab tests were indicative of severe hemolytic anemia and thrombocytopenia. Her renal function was continuously normal. As other causes of hemolysis and autoimmune diseases were excluded, a diagnosis of Evan’s syndrome was made although the Coombs’ test was negative. She showed partial response to high-dosage of prednisolone and IgG with increased but not normal platelet count and her fever disappeared. After transfusion of packed RBC and platelets, her symptoms and signs of the central nervous system disappeared and the fetus was removed through cesarean section. 22 days later, she underwent an emergent exploratory laparotomy confirming acute necrotic cholecystitis under supportive transfusion, and splenectomy was also performed. But the hemolytic anemia and thrombocytopenia still went on although she was still administered prednisolone and high-dosage of IgG. As a diagnosis of TTP was suspected, she received plasma exchange. The next day, her Hb level increase to 97g/L and her platelet count increased to 500×109/L without transfusion. More than one month later, her plasma sample was sent to another center to detect ADAMTS13 level and was found to be deficient in ADAMTS13 (7%). But antibody to ADAMTS13 was not detected. Conclusion: The cause of anemia and thrombocytopenia in this case was pregnancy associated TTP. Further experiment for detection of mutation in her ADAMTS13 gene is being done. Mis-diagnosis in this case may be related to lack of recognition of variation in the course, precipitating factors of the disease and unavailability of ADAMTS13 level test.

Platelet transfusion and catheter insertion for plasma exchange in patients with thrombotic thrombocytopenic purpura and a low platelet count

Transfusion ◽  
2015 ◽  
Vol 55 (7) ◽  
pp. 1798-1802 ◽  
Author(s):  
Etienne Riviere ◽  
Mélanie Saint-Léger ◽  
Chloé James ◽  
Yahsou Delmas ◽  
Benjamin Clouzeau ◽  
...  
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Platelet Transfusion ◽  
Catheter Insertion ◽  
Thrombocytopenic Purpura ◽  
Low Platelet Count

scholarly journals Acquired Deficiency of von Willebrand Factor-Cleaving Protease in a Patient With Thrombotic Thrombocytopenic Purpura

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2839-2846 ◽  
Author(s):  
Miha Furlan ◽  
Rodolfo Robles ◽  
Max Solenthaler ◽  
Bernhard Lämmle
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Protease Activity ◽  
Temporary Increase ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Plasma of patients with thrombotic thrombocytopenic purpura (TTP) has been shown to contain unusually large von Willebrand factor (vWF) multimers that may cause platelet agglutination in vivo. Fresh frozen plasma infusions and plasma exchange represent the most efficient therapy of acute TTP. A specific protease responsible for cleavage of vWF multimers has been recently isolated from normal human plasma and was found to be deficient in four patients with chronic relapsing TTP. We examined the activity of the vWF-cleaving protease in plasma samples collected over a period of 400 days from a further patient with recurrent episodes of TTP who was treated by plasma exchange, plasma infusion, vincristine, corticosteroid therapy, and splenectomy. Complete deficiency of the vWF-cleaving protease was established during the first episode of TTP. The ensuing normalization of the platelet count was associated with the appearance of the protease activity. Three months after remission from the initial TTP event, the vWF-cleaving protease again disappeared and the platelet count gradually decreased. Relapses of severe thrombocytopenia occurred 7 and 11 months after the first acute episode of TTP. Deficient protease activity was associated with the presence in the patient plasma of an inhibitor that was found to be an IgG. Plasma exchange/infusion was followed by a temporary increase in the antibody titer, whereas treatment with vincristine led to a recovery of the platelet count without affecting the inhibitor concentration. Splenectomy and corticosteroid treatment resulted in disappearance of the autoantibody and normalization of the protease activity and of the platelet count. Our data suggest that the thrombocytopenia in this patient with TTP was associated with a lack of the vWF-cleaving protease activity depleted by an autoimmune mechanism. This case, together with our previously reported patients, leads us to conclude that acquired as well as constitutional deficiency of the vWF-cleaving protease may predispose to TTP.

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