COVID-19 as a Potential Trigger for Immune Thrombotic Thrombocytopenic Purpura and Reason for an Unusual Treatment: A Case Report

2021 ◽  
Author(s):  
Marie-Kristin Schwaegermann ◽  
Lukas Hobohm ◽  
Johanna Rausch ◽  
Michael Reuter ◽  
Thomas-Friedrich Griemert ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Immunosuppressive Treatment ◽  
Autoimmune Disorder ◽  
Treatment Modalities ◽  
Therapeutic Drug ◽  
Thrombocytopenic Purpura ◽  
Tissue Ischemia ◽  
Platelet Receptor ◽  
Life Threatening ◽  
A Disintegrin And Metalloproteinase

AbstractImmune thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder characterized by severely reduced activity of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) due to autoantibodies. This leads to the development of pathogenic multimers of VWF, causing a thrombotic microangiopathy with decreased number of platelets, hemolysis, and life-threatening tissue ischemia of mostly brain, heart, and kidneys. Standard treatment of iTTP involves daily plasma exchange to remove ultra large multimers of VWF, inhibitors, substituting ADAMTS13, and the accompaniment of an immunosuppressive treatment with steroids. Recently, caplacizumab was approved for iTTP. Caplacizumab is a nanobody binding the A1 domain of VWF, blocking its interaction with glycoprotein Ib–IX–V platelet receptor and therefore preventing platelet aggregation. VWF activities may serve as therapeutic drug monitoring of caplacizumab, whereas ADAMTS13 activities may be used for biomarkers to guide caplacizumab treatment modalities and overall treatment duration. Additional immunosuppressive treatment by inhibiting autoantibody formation (e.g., the use of Rituximab, a chimeric monoclonal antibody directed against the B-cell antigen CD20) is a further treatment option. Infections are well-known causes for an acute episode for patients with iTTP. The novel SARS-CoV-2 virus is mainly associated with acute respiratory distress as well as diffuse endothelial inflammation and increased coagulopathy. However, little is known about an infection with SARS-CoV-2 virus triggering iTTP relapses. We herein report the case of an acute iTTP episode accompanying a SARS-CoV-2 infection.

Pembrolizumab-induced thrombotic thrombocytopenic purpura

2019 ◽  
Vol 26 (5) ◽  
pp. 1237-1240 ◽  
Author(s):  
Marcus SR Dickey ◽  
Anant J Raina ◽  
Peter J Gilbar ◽  
Brendan L Wisniowski ◽  
Joel T Collins ◽  
...  
Keyword(s):  
Adverse Events ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Oral Prednisolone ◽  
Autoimmune Disorder ◽  
Community Acquired Pneumonia ◽  
Thrombocytopenic Purpura ◽  
Life Threatening

Introduction Pembrolizumab is a humanised monoclonal antibody targeting the receptor programmed cell death protein-1 (PD-1), with anti-tumour activity demonstrated for many malignancies. Such immune checkpoint inhibitors are associated with many immune-related adverse events including rash, colitis, hepatitis, pneumonitis, endocrinopathy and, rarely, haematological adverse events, including immune-related thrombocytopenia. Case report We report a 60-year-old female with metastatic non-small cell lung cancer treated with pembrolizumab every three weeks. Following her fifth cycle, she presented to our hospital with community-acquired pneumonia. Thrombocytopenia developed the next day and, after detailed investigations, thrombotic thrombocytopenic purpura was diagnosed. Management and outcome Pembrolizumab was immediately ceased and plasma exchange commenced along with IV methylprednisolone 250 mg daily for three days followed by oral prednisolone. After five days of plasma exchange, platelet counts normalised and haemolytic anaemia resolved. Discussion Acquired thrombotic thrombocytopenic purpura is an autoimmune disorder caused by an inhibitory autoantibody against ADAMTS-13. While most cases of acquired thrombotic thrombocytopenic purpura are idiopathic, certain conditions (e.g. bacterial infection, autoimmune disorders, malignancies) and medications are associated with thrombotic thrombocytopenic purpura. Other potential causes were eliminated in our patient. As acquired thrombotic thrombocytopenic purpura is an autoimmune disorder, pembrolizumab, given its unique mechanism of action and association with immune-related adverse events, is believed to be implicated in the development of thrombotic thrombocytopenic purpura. This case is one of only two linking anti-PD-1 therapy to thrombotic thrombocytopenic purpura development (the other occurring in a patient on nivolumab plus ipilimumab). Thrombotic thrombocytopenic purpura is life-threatening and clinicians are advised to be aware of its possible occurrence in immune checkpoint inhibitor-treated patients.

scholarly journals Congenital thrombotic thrombocytopenic purpura presenting in adulthood with recurrent cerebrovascular events

2019 ◽  
Vol 12 (10) ◽  
pp. e229481
Author(s):  
Emma Tenison ◽  
Ashar Asif ◽  
Mathew Sheridan
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Fresh Frozen Plasma ◽  
Vessel Occlusion ◽  
Thrombocytopenic Purpura ◽  
Antibody Titres ◽  
Fresh Frozen ◽  
Life Threatening ◽  
History Of ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
A Disintegrin And Metalloproteinase

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, life-threatening disease, characterised by episodes of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and small vessel thrombosis. We describe a case of cTTP first diagnosed at age 70 years in a female presenting with an acute ischaemic stroke and thrombocytopenia, in whom A Disintegrin And Metalloproteinase with a Thrombospondin type 1 Motif, member 13 (ADAMTS13) levels were <10%, suggestive of thrombotic thrombocytopaenic purpura (TTP). The patient underwent plasma exchange and started rituximab for presumed immune TTP; however, anti-ADAMTS13 antibody titres were negative on two occasions. This, together with a history of pregnancies complicated by presumed disseminated intravascular coagulation, and two previous episodes of sepsis with MAHA, prompted investigation for cTTP, which was confirmed by genetic testing. Despite treatment with infusions of solvent/detergent-treated, virus-inactivated fresh frozen plasma, she has re-presented with further neurological deficit, associated with new infarcts on imaging. cTTP has a varied phenotype which, as demonstrated in this case, can include large vessel occlusion.

scholarly journals Alternate-Day Dosing of Caplacizumab for Immune-Mediated Thrombotic Thrombocytopenic Purpura

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2087-2087
Author(s):  
Lucas Kühne ◽  
Dennis A. Eichenauer ◽  
Paul Knöbl ◽  
Linus A. Völker ◽  
Jessica Kaufeld ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Autoimmune Disorder ◽  
Daily Treatment ◽  
Treatment Modalities ◽  
Close Monitoring ◽  
Dosing Regimen ◽  
Thrombocytopenic Purpura ◽  
Normal Platelet ◽  
Immune Mediated ◽  
Risk Patients

Abstract Background: The anti-VWF nanobody caplacizumab directly prevents the fatal microthrombi formation in immune-mediated thrombotic thrombocytopenic purpura, thereby adding a new therapeutic principle to the treatment of this autoimmune disorder. However, real-world treatment modalities beyond clinical trials remain heterogeneous. Methods: Here, we describe the risks and benefits of an alternate-day dosing regimen for caplacizumab, by thoroughly analyzing the timing and outcome of this treatment approach in a retrospective cohort of 25 iTTP patients treated with caplacizumab in Austria and Germany between 2018 and 2021. Results: Alternate-day dosing of caplacizumab appeared feasible and led to persisting normal platelet counts in the majority of patients, who were converted after a median time of 17 days daily treatment. Four patients experienced iTTP exacerbations or relapses that led to the resumption of daily caplacizumab application and/or other therapies. VWF activity was repeatedly measured in 17 out of 25 patients and documented sufficient suppression by caplacizumab after 24 and 48 hours, in line with published pharmacokinetics. Conclusion: Extension of caplacizumab injection intervals from daily to alternate-day dosing may be safely considered in selected patients after 30 days of daily treatment. Earlier modifications may be considered in low-risk patients, but require close monitoring for clinical and laboratory features of thrombotic microangiopathy. Disclosures Völker: Sanofi-Genzyme: Honoraria, Other: counselling fees.

Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease

2003 ◽  
Vol 82 (11) ◽  
pp. 702-704 ◽  
Author(s):  
H. E. Lee ◽  
V. J. Marder ◽  
L. J. Logan ◽  
S. Friedman ◽  
B. J. Miller
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Sickle Cell ◽  
Thrombocytopenic Purpura ◽  
Hemoglobin C ◽  
Life Threatening

scholarly journals Insights from the Hereditary Thrombotic Thrombocytopenic Purpura Registry: Discussion of Key Findings Based on Individual Cases from Switzerland

2020 ◽  
Vol 40 (S 01) ◽  
pp. S5-S14
Author(s):  
Johanna A. Kremer Hovinga ◽  
Thomas R. Braschler ◽  
Florian Buchkremer ◽  
Stefan Farese ◽  
Heinz Hengartner ◽  
...  
Keyword(s):  
Cohort Study ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disease Onset ◽  
Myocardial Infarctions ◽  
Thrombocytopenic Purpura ◽  
Blood Disorder ◽  
A Disintegrin And Metalloproteinase ◽  
Systematic Collection ◽  
Plasma Infusions

AbstractThe Hereditary TTP Registry is an international cohort study for patients with a confirmed or suspected diagnosis of hereditary thrombotic thrombocytopenic purpura (hTTP) and their family members. Hereditary TTP is an ultra-rare blood disorder (prevalence of ∼1–2 cases per million), the result of autosomal-recessively inherited congenital ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency (ADAMTS13 activity <10% of the normal), and associated with yet many unanswered questions. Until December 2017, the Hereditary TTP Registry had enrolled 123 confirmed hTTP patients. Their median age at disease onset was 4.5 years (range: 0–70) and at clinical diagnosis 16.7 years (range: 0–69), a difference that highlights the existing awareness gap in recognizing hTTP. The systematic collection of clinical data of individual patients revealed their substantial baseline comorbidities, as a consequence of recurring TTP episodes in the past. Most notable was the high proportion of patients having suffered from premature arterial thrombotic events, mainly transient ischemic attacks, ischemic strokes, and to a lesser extent myocardial infarctions. At 40 to 50 years of age and above, more than 50% of patients had suffered from at least one such event, and many had experienced arterial thrombotic events despite regular plasma infusions every 2 to 3 weeks that supplements the missing plasma ADAMTS13. The article by van Dorland et al. (Haematologica 2019;104(10):2107–2115) and the ongoing Hereditary TTP Registry cohort study were recognized with the Günter Landbeck Excellence Award at the 50th Hemophilia Symposium in Hamburg in November 2019, the reason to present the Hereditary TTP Registry in more detail here.

Thrombotic thrombocytopenic purpura: pathophysiology, treatment, and related nursing care

1995 ◽  
Vol 15 (6) ◽  
pp. 44-52
Author(s):  
M Kajs-Wyllie
Keyword(s):  
Critical Care ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Nursing Care ◽  
Critical Care Unit ◽  
Family Members ◽  
Vital Role ◽  
Critical Care Nurses ◽  
Thrombocytopenic Purpura ◽  
Rare Syndrome ◽  
Life Threatening

The patient diagnosed with TTP presents to the critical care unit with myriad life-threatening problems. Knowledge of the pathophysiology and treatment of this rare syndrome is essential to plan care appropriately. However, despite immediate diagnosis and intervention, the outcome may not be successful. Critical care nurses play a vital role in caring for these patients, as well as helping family members deal with this devastating disease.

scholarly journals How I treat thrombotic thrombocytopenic purpura in pregnancy

Blood ◽  
2020 ◽  
Vol 136 (19) ◽  
pp. 2125-2132
Author(s):  
Barbara Ferrari ◽  
Flora Peyvandi
Keyword(s):  
Differential Diagnosis ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Current Knowledge ◽  
Fetal Outcome ◽  
Subsequent Pregnancy ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Life Threatening ◽  
High Index Of Suspicion ◽  
In Pregnancy

Abstract Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening thrombotic microangiopathy (TMA) caused by acquired or congenital severe deficiency of ADAMTS13. Pregnancy is a recognized risk factor for precipitating acute (first or recurrent) episodes of TTP. Differential diagnosis with other TMAs is particularly difficult when the first TTP event occurs during pregnancy; a high index of suspicion and prompt recognition of TTP are essential for achieving a good maternal and fetal outcome. An accurate distinction between congenital and acquired cases of pregnancy-related TTP is mandatory for safe subsequent pregnancy planning. In this article, we summarize the current knowledge on pregnancy-associated TTP and describe how we manage TTP during pregnancy in our clinical practice.

scholarly journals Rituximab Twice Weekly for Refractory Thrombotic Thrombocytopenic Purpura in a Critically Ill Patient with Acute Respiratory Distress Syndrome

2020 ◽  
Vol 13 (1) ◽  
pp. 153-157
Author(s):  
Bahjat Azrieh ◽  
Arwa Alsaud ◽  
Khaldun Obeidat ◽  
Amr Ashour ◽  
Seham Elebbi ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Distress Syndrome ◽  
Standard Of Care ◽  
Critically Ill Patient ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Life Threatening

Thrombotic thrombocytopenic purpura (TTP) is a rare, serious, life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and hypercoagulability. The etiology is a deficiency of ADAMTS13 which is usually caused by acquired antibodies. Plasma exchange and steroids is the standard of care in the treatment of TTP. However, there are refractory cases of TTP which require further management. Rituximab appears to be a safe and effective therapy for refractory and relapsing TTP. Here we report a challenging case of TTP that responded to treatment with rituximab twice weekly. According to our knowledge, rituximab twice weekly has never been used for TTP before.

scholarly journals Thrombotic Thrombocytopenic Purpura Following Honeybee Envenomation: A Case Report

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Zahra Khalighi ◽  
Golnaz Azami ◽  
Elham Shafiei ◽  
Ali Sahebi ◽  
Aliashraf Mozafari
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Case Reports ◽  
Major Complication ◽  
The Body ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Toxic Reaction ◽  
Bee Sting ◽  
Life Threatening ◽  
Underlying Diseases

Background: Thrombotic Thrombocytopenic Purpura (TTP) is a rare and life-threatening disorder characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, fever, renal dysfunction, and neurological deficient. TTP leads to the formation of blood clots in small blood vessels throughout the body. TTP is associated with many risk factors such as pregnancy, HIV, cancer, lupus, and infections. Recently there have been few published case reports of bee sting associated TTP.Methods: A 67-year-old man from a rural area of the Southwest Province of Iran, Ilam, was referred to the academic general hospital because of fever, chills, sweating, vomiting and dizziness following the honeybee sting on his body. Results: this study showed that,multiple co-morbidities including CVD and diabetes, along with coagulation abnormalities after honeybee stings, seriously exacerbated patient hemodynamic status.Conclusion: TTP, as a major complication due to the toxic reaction of a large number of bee stings with underlying diseases in patients, should be given more attention.

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