Thrombotic Microangiopathy in Cancer

2019 ◽  
Vol 45 (04) ◽  
pp. 348-353 ◽  
Author(s):  
Ilene Ceil Weitz
Keyword(s):  
Platelet Count ◽  
Cancer Treatment ◽  
Hemolytic Anemia ◽  
Cancer Chemotherapy ◽  
Thrombotic Microangiopathy ◽  
Organ Damage ◽  
Microangiopathic Hemolytic Anemia ◽  
Therapeutic Modalities

AbstractThrombotic microangiopathy (TMA) is a rare but often devastating complication of cancer and cancer treatment. The syndrome is defined by thrombocytopenia (i.e., a platelet count of < 150,000/mcL or > 30% decrease from baseline), microangiopathic hemolytic anemia, and some evidence of organ damage. Among the nine recognized groups of disorders causing TMA, the focus of this article will be on cancer and cancer treatment-related causes of TMA. This review will discuss the pathophysiology of TMA in cancer, chemotherapy-associated TMA, transplant-associated TMA, and newer therapeutic modalities.

scholarly journals Differential diagnosis of obstetric thrombotic microangiopathy: a review

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Polina I. Kukina ◽  
Anastasiya V. Moskatlinova ◽  
Irina M. Bogomazova ◽  
Elena V. Timokhina
Keyword(s):  
Differential Diagnosis ◽  
Hemolytic Anemia ◽  
Thrombotic Microangiopathy ◽  
Hellp Syndrome ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
Microangiopathic Hemolytic Anemia ◽  
Atypical Hus ◽  
Obstetric Practice

Thrombotic microangiopathy (TMA) is a clinical and morphological syndrome, which is based on damage of the endothelium. Clinically, TMA is characterized by a triad of symptoms: thrombocytopenia, microangiopathic hemolytic anemia, and target organ damage. In obstetric practice, TMA most often occurs with preeclampsia or HELLP syndrome, atypical HUS, TTP. The review presents the basic differential criteria for the diagnosis of TMA during pregnancy and after childbirth, as well as the management of patients.

Thrombotic thrombocytopenic purpura with typical pentalogy in a child: a case report and literature review

2021 ◽  
Author(s):  
Qian Wan ◽  
Yao Ye ◽  
Xiaohong Zhong ◽  
Zhongjin Xu ◽  
Jian Li
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Renal Insufficiency ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Thrombotic Microangiopathy ◽  
Typical Case ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Life Threatening

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy with clinical quintuple symptoms, including fever, thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, and renal insufficiency. TTP onset in children is rare, and the percentage of acute TTP with these five symptoms at the same time is <10%. In this study, we reported a typical case of TTP onset in a child with clinical quintuple symptoms.

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.)

Thrombotic Microangiopathy in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5317-5317 ◽  
Author(s):  
Jennifer Yui ◽  
Jan Van Keer ◽  
Ravi Vij ◽  
Kenar Jhaveri ◽  
Efstathios Kastritis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hemolytic Anemia ◽  
Thrombotic Microangiopathy ◽  
Research Funding ◽  
Proteasome Inhibitors ◽  
Temporal Correlation ◽  
Organ Damage ◽  
Initial Presentation ◽  
Hematopoietic Stem ◽  
Cell Transplants

Abstract Background: Thrombotic microangiopathy (TMA) is a hematologic syndrome associated with endothelial injury, microvascular thrombosis, and hemolytic anemia resulting in end organ damage. TMA is rarely associated with multiple myeloma (MM) and is usually reported in the setting of allogeneic hematopoietic stem cell transplants (AHSCT), with associated graft versus host disease and calcineurin inhibitor use. We present 11 cases of TMA in MM patients not associated with AHSCT. Methods: Cases were collected from multiple centers in patients with confirmed diagnosis of MM. TMA was diagnosed by the presence of thrombocytopenia and evidence of microangiopathic hemolytic anemia. Results: Eleven patients with MM were identified to have developed TMA during the course of their disease. Two patients presented with TMA at the time of MM diagnosis. A third had been off treatment for over a year prior to presenting with a TMA which correlated with a significant increase in her free light chains. The other cases occurred during active treatment. All remaining patients received proteasome inhibitors, with three patients on bortezomib-based regimens and five patients on carfilzomib. One patient on a bortezomib-based regimen had been stable prior to developing a TMA in the setting of sepsis. In the remaining patients, the TMA developed rapidly after initiating the proteasome inhibitor. In all cases, the TMA improved after drug withdrawal. One patient was later rechallenged with bortezomib and again developed TMA. Discussion: A review of the literature reveals only nine cases of TMA with MM. Of these, 4 patients had TMA as the initial presentation of MM, and 5 patients were on treatment, most often bortezomib-based regimens. Our series patients match those in the literature closely and demonstrate that TMAs can occur in MM outside of the context of AHSCT. In roughly one third of patients, TMAs were the initial presentation of MM and improved with treatment of the MM. In others, the use of proteasome inhibitors appears to be associated with development of TMA. In these cases, the temporal correlation, resolution of TMA after medication withdrawal, and the instance of recurrence of TMA with rechallenge of bortezomib, support a causal relationship between the medication and the TMA. Thus, a high clinical suspicion for TMA must exist for patients on proteasome inhibitors who develop worsening anemia and thrombocytopenia. Medication should be withdrawn if TMA is diagnosed. Disclosures Vij: Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy; Takeda: Consultancy, Research Funding; Novartis: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Merck: Consultancy.

scholarly journals Thrombocytopenia and Microangiopathic Hemolytic Anemia Precipitated By Acute Pancreatitis: A Single Center Experience of Five Cases

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1377-1377 ◽  
Author(s):  
Mary Salib ◽  
Anne-Sophie Lemay ◽  
Megan Buchholz ◽  
Katerina Pavenski
Keyword(s):  
Acute Pancreatitis ◽  
Platelet Count ◽  
Hemolytic Anemia ◽  
High Dose ◽  
Significant Heterogeneity ◽  
Adamts13 Activity ◽  
Microangiopathic Hemolytic Anemia ◽  
Complement Protein ◽  
Advisory Boards ◽  
Adamts13 Deficiency

Abstract Introduction Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic disorder characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. It has been associated with a deficiency or dysfunction of ADAMTS13, an enzyme responsible for cleaving ultra-large von Willebrand factor multimers, thus preventing spontaneous platelet adhesion and aggregation. In its absence, platelet aggregates accumulate in the microvasculature causing neurological symptoms, cardiac ischemia and renal dysfunction. Most cases in adults are idiopathic, and associated with severe ADAMTS13 deficiency (<10%) and anti-ADAMTS13 antibodies. Acquired TTP due to various conditions, such as HIV, drugs, malignancy, collagen disease, bone marrow transplant and acute pancreatitis (AP), have also been described. Some cases of these secondary TTP may be associated with no to moderate ADAMTS13 deficiency and are referred to as thrombotic microangiopathies (TMAs). If plasma exchange (PLEX) has been the treatment of choice for acquired TTP, it has not been shown to be very effective for TMAs. AP-associated MAHA and thrombocytopenia (MAHA-T) might be one exception. Methods To better understand the relationship between AP and MAHA-T and to evaluate its response to PLEX, we retrospectively reviewed all cases of suspected TTP/ MAHA-T treated by PLEX in the context of AP in our institution from 2005 to 2015. For the purpose of this report, we preferred to use the term MAHA-T to describe this phenomenon since TMA usually refers to a pathologic diagnosis. Finally, a literature review of published cases was also performed. Results Five patients were treated with PLEX for suspicion of TTP in the context of AP between January 1st, 2005 and December 31st, 2015 at our centre. Median age was 36 (31-60). Etiologies for pancreatitis were alcohol (3/5) or idiopathic (2/5). Peak lipase level ranged between 426 and 5853 U/L. One patient had 3 episodes of MAHA-T following AP, always in the context of alcohol abuse. Two patients had evidence of MAHA-T on admission, while the remaining 3 patients had an unremarkable CBC at presentation followed by an abrupt drop in platelet count (nadir, 9-23 x 109/L). All patients showed simultaneously signs of MAHA (Hb nadir between 47 and 93 g/L) with fragmentation on the blood smear and abnormal hemolytic parameters: LD level 1104-8097 U/L, bilirubin 36-176 umol/L, reticulocyte count 130-541 x109/L and undetectable haptoglobin. The median time from AP presentation to the development of laboratory or clinical features of MAHA-T in these cases was 2 days (1-3). Acute kidney injury was present in all cases with creatinine levels ranging between 118-906 umol/L. One patient required hemodialysis. Other observed end organ damage included neurologic symptoms (3/5 patients), elevated troponin (5/5 patients) and transaminitis (4/5). One patient experienced a cardiac arrest. All patients had ADAMTS13 activity measured. One patient had severe deficiency on two separate episodes (ADAMTS13 was <1% and 6% respectively). Three other patients had normal ADAMTS13 activity (average 69%) and one had a moderate deficiency by a qualitative assay. In 4 patients, where tests were performed, there was significant heterogeneity in complement protein and function studies between patients ranging from normal to depressed C3 and C4 and normal to elevated CH50. Complement genetics screen was performed in 3 cases and was normal in all 3 cases. PLEX was initiated in all patients and remission (platelet count over 150 x 109/L) was seen for all after a median of 10 daily treatments (2-12). High dose steroids were used in 4 patients. All patients survived to discharge and completely recovered their kidney function. Conclusion TTP/MAHA-T precipitated by AP is increasingly recognized and more than 40 cases have been described in the literature. Similar to our findings, time to MAHA-T occurrence is generally reported within the first 4 days after admission for AP, often when markers for pancreatitis are improving, and most patients do not have severe ADAMTS13 deficiency. While many have looked at ADAMTS13 level, to our knowledge, none have yet reported thorough complement studies and genetics. The 3 cases described herein are then the first cases suggesting this is not a complement mediated disorder. Finally, our review and cases confirm that PLEX is effective and prognosis is good in almost all cases. Disclosures Pavenski: Alexion Pharmaceuticals Inc.: Honoraria, Other: attended an entity's advisory boards.

scholarly journals Caplacizumab As Step-up Therapy in Refractory TTP Utilizing Adamts-13 Activity and Evidence of End-Organ Damage

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4909-4909
Author(s):  
Neel Belani ◽  
Adriel Barrios-Anderson ◽  
William Rafelson ◽  
Matthew I. Quesenberry ◽  
Rabin Niroula
Keyword(s):  
Plasma Exchange ◽  
Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Organ Damage ◽  
Vitamin B ◽  
Adamts13 Activity ◽  
Microangiopathic Hemolytic Anemia ◽  
End Organ Damage ◽  
B12 Deficiency ◽  
Vitamin B 12

Background: Thrombotic Thrombocytopenic Purpura (TTP) is a form of microangiopathic hemolytic anemia that is classically characterized by the clinical pentad of fever, hemolytic anemia, thrombocytopenia, renal dysfunction, and neurologic dysfunction. The pathophysiology of acquired TTP is marked by autoantibody formation against ADAMSTS13, an enzyme responsible for breaking down von Willebrand Factor (vWF) multimers. Standard therapy for TTP includes both replenishing functional ADAMTS-13 and immune-modulation with plasma-exchange and steroids/rituximab, respectively. A novel therapy addresses the microvascular thrombosis hallmark of end-organ damage in TTP. Caplacizumab, a humanized immune globulin that inhibits vWF interaction with platelets, achieved its primary endpoint of faster time to platelet normalization than placebo in the Stage 3 HERCULES trial when given up-front with additional standard therapies. Case Summary: A previously health 26-year-old G3P2 female presented to the ED at 38 weeks gestation with fatigue and confusion. She was found to have a platelet count of 5,000 per microliter, hematocrit of 18.6%, lactate dehydrogenase (LDH) of 1,750 IU/L, and haptoglobin of 11mg/dL. Peripheral blood smear was remarkable for evidence of microangiopathic hemolytic anemia. She had a normal serum creatinine. She was diagnosed clinically with TTP and subsequently underwent emergent caesarian section. She was started on plasma exchange given her ADAMTS13 activity of 6% and features of severe TTP. Her neurological status and platelets initially responded well to plasmapheresis (PE) at 1x volume alone; however, on Day 6 her platelets decreased from 97,000 to 15,000 per microliter. This prompted initiation of both steroids, weekly rituximab and increasing PE to 1.5 x. She continued to be refractory and acutely declined on Day 7, during which she developed worsening headaches followed by seizure, renal failure with proteinuria, uncontrolled hypertension and increasing hemolysis. She required ICU admission and one session of hemodialysis. Despite increasing PE, steroids and rituxan, the patient's inhibitor peaked to 142 U/ml with an ADAMTS-13 activity of 0% on Day 9. PE was increased to 1.5 x volume twice daily. Caplacizumab was obtained and initiated on Day 10. Her platelets on Day 11 were at their nadir of 4,000 per microliter, with an inhibitor of 93.9 and an ADAMTS-13 activity of 0%. She remained in the ICU, where her mental status, renal function improved gradually. She was found with a reticulocyte index of 1.29, for which she was treated with Vitamin B-12 for a methylmalonic acid level of 798 nmol/L (range 87-318 nmol/L) and a low normal level of vitamin B-12. PE was stopped on Day 22 after confirming her platelet level remained >150,000 per microliter for more than three days. Her course was further complicated by aspiration, parainfluenza 3, MSSA bacteremia, and E Coli UTI, for which she received antibiotics and supportive treatment. She completed four cycles of rituximab on Day 27, and was discharged to home with a steroid taper and an additional 21 days of caplacizumab. She was readmitted three times during those 21 days for hemiplegic migraines. She achieved remission with normal complete blood count and ADAMTS13 >109% with an inhibitor 3 on Day 54, after which she was administered her last dose of caplacizumab on Day 56. Discussion: We detail the clinical and treatment course in our patient with severe, acquired TTP from pregnancy. Our timing of caplacizumab administration differed from that in the HERCULES Trial. Rather than administering caplacizumab at the onset of diagnosis, we utilized markers of end-organ damage, ADAMTS13 activity and inhibitor level to gauge the trajectory of the disease process before administering additional therapies. This may represent an alternative approach to treating aTTP in a post-caesarian patient given concern for risk of bleeding and lack of trial data that adequately captures the bleeding risk of this sub-population. Lastly, we describe reticulocytopenia and Vitamin B12 deficiency in this patient complicating her recovery from TTP. The etiology of her B12 deficiency is still unclear ( anti-parietal antibody titer <1:120). Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Mild thrombocytopenia indicating maternal organ damage in pre‐eclampsia: a cross‐sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Michinori Mayama ◽  
Mamoru Morikawa ◽  
Takashi Yamada ◽  
Takeshi Umazume ◽  
Kiwamu Noshiro ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Platelet Count ◽  
Intensive Care Unit Admission ◽  
Neonatal Intensive Care Unit ◽  
Preterm Delivery ◽  
Neonatal Intensive Care ◽  
Organ Damage ◽  
Severe Thrombocytopenia ◽  
Relative Risks

Abstract Background Currently, there is a disagreement between guidelines regarding platelet count cut-off values as a sign of maternal organ damage in pre-eclampsia; the American College of Obstetricians and Gynecologists guidelines state a cut-off value of < 100 × 109/L; however, the International Society for the Study of Hypertension in Pregnancy guidelines specify a cut-off of < 150 × 109/L. We evaluated the effect of mild thrombocytopenia: platelet count < 150 × 109/L and ≥ 100 × 109/L on clinical features of pre-eclampsia to examine whether mild thrombocytopenia reflects maternal organ damage in pre-eclampsia. Methods A total of 264 women were enrolled in this study. Participants were divided into three groups based on platelet count levels at delivery: normal, ≥ 150 × 109/L; mild thrombocytopenia, < 150 × 109/L and ≥ 100 × 109/L; and severe thrombocytopenia, < 100 × 109/L. Risk of severe hypertension, utero-placental dysfunction, maternal organ damage, preterm delivery, and neonatal intensive care unit admission were analyzed based on platelet count levels. Estimated relative risk was calculated with a Poisson regression analysis with a robust error. Results Platelet counts indicated normal levels in 189 patients, mild thrombocytopenia in 51 patients, and severe thrombocytopenia in 24 patients. The estimated relative risks of severe thrombocytopenia were 4.46 [95 % confidence interval, 2.59–7.68] for maternal organ damage except for thrombocytopenia, 1.61 [1.06–2.45] for preterm delivery < 34 gestational weeks, and 1.35 [1.06–1.73] for neonatal intensive care unit admission. On the other hand, the estimated relative risks of mild thrombocytopenia were 0.97 [0.41–2.26] for maternal organ damage except for thrombocytopenia, 0.91 [0.62–1.35] for preterm delivery < 34 gestational weeks, and 0.97 [0.76–1.24] for neonatal intensive care unit admission. Conclusions Mild thrombocytopenia was not associated with severe features of pre-eclampsia and would not be suitable as a sign of maternal organ damage.

scholarly journals Streptococcus pneumoniae-associated thrombotic microangiopathy in an immunosuppressed adult

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 204-210 ◽  
Author(s):  
Yumi Ichikawa ◽  
Masato Murata ◽  
Makoto Aoki ◽  
Jun Nakajima ◽  
Yuta Isshiki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Streptococcus Pneumoniae ◽  
Blood Culture ◽  
Renal Dysfunction ◽  
Hemolytic Anemia ◽  
Thrombotic Microangiopathy ◽  
Detailed Examination ◽  
Adamts13 Activity ◽  
Adult Case

AbstractA 62-year-old male who was receiving prednisolone and methotrexate for scleroderma and rheumatoid arthritis complained of diarrhea and vomiting, and was transferred to our hospital for detailed examination and treatment of renal dysfunction and thrombocytopenia. Hemolytic anemia and crushed erythrocytes were found during the patient’s course; therefore, we suspected thrombotic microangiopathy (TMA). His ADAMTS13 activity was 60.3% and his ADAMTS13 inhibitor was under 0.5. In addition, his blood culture was positive for Streptococcus pneumoniae, and we finally diagnosed Streptococcus pneumoniae-associated TMA (pTMA). The patient was treated with antibiotics and hemodialysis. The patient recovered and was discharged on the 45th hospital day. Adult pTMA cases are remarkably rare. We herein report a successfully treated adult case of pTMA.

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