scholarly journals Refractory vaccine-induced thrombotic thrombocytopenia (VITT) managed with delayed therapeutic plasma exchange (TPE)

2021 ◽  
Author(s):  
Ajay Major ◽  
Timothy Carll ◽  
Clarence W. Chan ◽  
Chancey Christenson ◽  
Geoffrey D. Wool ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Alcoholic Cirrhosis ◽  
Therapeutic Plasma Exchange ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Sustained Improvement ◽  
Vein Thrombosis ◽  
Hematologic Disorder

Abstract Vaccine-induced thrombotic thrombocytopenia (VITT) is a newly-described hematologic disorder which presents as acute thrombocytopenia and thrombosis after administration of adenovirus-based vaccines against COVID-19. Due to positive assays for antibodies against platelet factor 4 (PF4), VITT is managed similarly to autoimmune heparin-induced thrombocytopenia (HIT) with intravenous immunoglobulin (IVIG) and non-heparinoid anticoagulation. We describe a case of VITT in a 50-year-old man with antecedent alcoholic cirrhosis who presented with platelets of 7 × 103/µL and portal vein thrombosis 21 days following administration of the Ad26.COV2.S COVID-19 vaccine. The patient developed progressive thrombosis and persistent severe thrombocytopenia despite IVIG, rituximab and high-dose steroids and had persistent anti-PF4 antibodies over 30 days after his initial presentation. As such, delayed therapeutic plasma exchange (TPE) was pursued as salvage therapy, with a rapid and sustained improvement in his platelet count. Our case serves as proof-of-concept of the efficacy of TPE in VITT.

A Successful Venous Thromboprophylaxis in a Patient with Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT): a case report of the first reported case in Thailand

2021 ◽  
Author(s):  
Archrob Khuhapinant ◽  
Tarinee Rungjirajittranon ◽  
Bundarika Suwanawiboon ◽  
Yingyong Chinthammitr ◽  
Theera Ruchutrakool
Keyword(s):  
Asian Population ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Imaging Studies ◽  
Fatal Complication ◽  
Platelet Factor ◽  
High Dose Dexamethasone ◽  
Prophylactic Dose ◽  
Spontaneous Platelet Aggregation ◽  
Very High

Abstract BackgroundVaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but fatal complication of Coronavirus Disease 2019 vaccine. Many reports of VITT have mostly been in the Caucasian population. Here, we present first reported case from an oriental population.Case presentationA 26-year-old female who had severe headache and severe thrombocytopenia 8 days after administration of the ChAdOx1 nCoV-19 vaccine developed by AstraZeneca. Although no thrombosis was demonstrated by imaging studies, she had very highly elevated d-dimer level during hospitalization. Serology for antibody against platelet factor 4 was positive on several days with very high optical density readings. Furthermore, we found the antibody could induce spontaneous platelet aggregation without the presence of heparin. We decided to treat her with intravenous immunoglobulin, high-dose dexamethasone, and a prophylactic dose of apixaban. She improved rapidly and was discharged from the hospital 6 days after admission. Neither thrombocytopenia nor thrombosis was subsequently detected at three weeks follow-up.ConclusionsDespite lower rate of thrombosis, VITT can present in Asian population. Early detection and prompt treatment of VITT can improve patients’ clinical outcome. Thromboprophylaxis of non-heparin anticoagulants also results in prevention of clot formation.

Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel
Keyword(s):  
Platelet Count ◽  
Heparin Therapy ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Increased Risk ◽  
Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

scholarly journals Successful Treatment of Vaccine-Induced Immune Thrombotic Thrombocytopenia in a 26-Year-Old Female Patient

2021 ◽  
pp. 1-4
Author(s):  
Marcel Kemper ◽  
Georg Lenz ◽  
Rolf Michael Mesters
Keyword(s):  
Female Patient ◽  
Treatment Options ◽  
Anticoagulation Therapy ◽  
Intravenous Immunoglobulins ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Vein Thrombosis ◽  
Medical Facilities ◽  
Deep Vein ◽  
Improve Patient

Vaccine-induced immune thrombotic thrombocytopenia (VITT) has already been described after vaccination with ChAdOx2 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen). However, less knowledge so far has been gained about optimal therapeutic regimens in VITT-suspected patients. Here, we report the case of a 26-year-old female patient, who developed bilateral deep vein thrombosis in the lower legs and severe thrombocytopenia after ChAdOx2 nCov-19 vaccination. After initial anticoagulation therapy regimens including fondaparinux, apixaban, and danaparoid failed, the patient was successfully treated with high-dose intravenous immunoglobulins in combination with parental anticoagulation therapy with argatroban. As vaccination against severe acute respiratory syndrome coronavirus 2 affects billions of people worldwide, medical facilities and hospitals have to be prepared and provide effective treatment options in VITT-suspected patients, including rapid application of high-dose intravenous immunoglobulins, to improve patient outcomes.

scholarly journals A Case of Heparin-Induced Thrombocytopenia That Developed in the Therapeutic Course of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Taketoshi Nonaka ◽  
Makoto Harada ◽  
Masahiko Sumi ◽  
Wataru Ishii ◽  
Tohru Ichikawa ◽  
...  
Keyword(s):  
Clinical Course ◽  
Systemic Vasculitis ◽  
Platelet Factor 4 ◽  
Organ Injury ◽  
Platelet Factor ◽  
Immunological Mechanism ◽  
Heparin Induced Thrombocytopenia ◽  
Vein Thrombosis ◽  
Leg Edema ◽  
Rapidly Progressive Renal Failure

Background. Heparin-induced thrombocytopenia (HIT) causes thrombocytopenia via an immunological mechanism, resulting in severe organ injury due to arterial-venous thrombosis. HIT often develops in hemodialysis patients owing to heparin use. Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic vasculitis, and cases of AAV complicated with HIT are rare. In addition, it mostly occurs in patients undergoing hemodialysis. Case Presentation. An 87-year-old woman presented with rapidly progressive renal failure and severe leg edema. She was diagnosed with AAV and treated with glucocorticoid and heparin calcium to prevent deep vein thrombosis. Eight days after the start of heparin calcium, her platelet count decreased and the anti-platelet factor 4-heparin complex antibody was strongly positive (>5.0 U/mL; the cutoff point of the anti-platelet factor 4-heparin complex antibody evaluated by the latex turbidity assay is 1.0 U/mL). She was diagnosed with HIT and treated with argatroban. Subsequently, her platelet counts increased gradually. Conclusion. We encountered a case of HIT that developed prior to the induction of hemodialysis in the clinical course of AAV. When AAV clinical course presents thrombocytopenia, the possibility of HIT should be considered.

Thienopyridine-Associated Thrombotic Thrombocytopenia Purpura: Updated Antibody Results From the SERF-TTP Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 892-892
Author(s):  
Anaadriana Zakarija ◽  
Thanh Ha Luu ◽  
Hau C. Kwaan ◽  
June McKoy ◽  
Ivy Weiss ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Neutralizing Antibodies ◽  
Conflicts Of Interest ◽  
Therapeutic Plasma Exchange ◽  
Severe Thrombocytopenia ◽  
Adamts13 Activity ◽  
Laboratory Findings ◽  
History Of ◽  
Adamts13 Deficiency ◽  
Drug Dependent

Abstract Abstract 892 Background: The thienopyridines, ticlopidine and clopidogrel, have been associated with thrombotic thrombocytopenia purpura (TTP). However, few studies have reported information on antibodies to ADAMTS13 among patients with thienopyridine-associated TTP. We previously reported on two mechanistic pathways of thienopyridine-associated TTP with some overlapping features. Evaluation of ADAMTS13 autoantibodies was undertaken to improve understanding of these syndromes. Methods: Clinical and laboratory findings were evaluated for 30 ticlopidine-, 10 clopidogrel-associated TTP cases, and 54 cases of idiopathic TTP. Results: Among patients with thienopyridine-induced TTP, those with a history of ticlopidine versus clopidogrel use were more likely to present with severe thrombocytopenia (platelet < 20,000) (90% versus 13%), severe ADAMTS13-deficiency (80% versus 0%), and neutralizing antibodies to ADAMTS13 (100% versus 0%), and were less likely to have less than a two week history of thienopyridine exposure (0% versus 50%) (p<0.05 for each comparison). They were also more likely to survive following therapeutic plasma exchange (TPE) (85% versus 50%). 2 patients exposed to clopidogrel later relapsed and had similar characteristics to idiopathic TTP patients with non-deficient ADAMTS13 activity. Conclusion: Ticlopidine causes TTP by a pathway involving a neutralizing autoantibody to ADAMTS13 while clopidogrel causes TTP by an ADAMTS13-independent pathway. Although ADAMTS13 autoantibodies are present in both idiopathic and ticlopidine-associated TTP, spontaneous relapses are not seen in ticlopidine-associaated TTP, suggesting that drug-dependent antibodies are present. Clopidogrel associated TTP is distinct from idiopathic TTP in that ADAMTS13 autoantibodies are absent and response to TPE is poor. Disclosures: No relevant conflicts of interest to declare.

Incidence of Isolated Heparin-Induced Thrombocytopenia and the Risk of Developing Subsequent Thrombosis Using the New IgG Specific Anti-PF4/Heparin ELISA

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1448-1448
Author(s):  
Sofyan M. Radaideh ◽  
Eugene P. Frenkel ◽  
Ravindra Sarode ◽  
Yu-Min Shen
Keyword(s):  
Conflicts Of Interest ◽  
Clinical Findings ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
High Dose ◽  
Elisa Assay ◽  
Initial Manifestation ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Number Of Patients

Abstract Abstract 1448 BACKGROUND: The new IgG specific ELISA for anti-platelet factor 4 (PF4)/heparin antibody is recently introduced for the diagnosis of heparin-induced thrombocytopenia (HIT). It is as sensitive but more specific than the poly-specific IgG, M, A ELISA. About 50% of patients testing positive for the anti-PF4/heparin antibody have thrombocytopenia alone as initial manifestation of HIT without thrombosis (isolated HIT). These patients are thought to be at high risk (≂f30%) for developing thrombosis within next 28 days. The incidence of isolated HIT using IgG-specific ELISA is unknown. OBJECTIVES: Evaluate the incidence of isolated HIT using the IgG specific anti-PF4/heparin ELISA and the risk of developing subsequent thrombosis in these patients. PATIENTS AND METHODS: We performed a retrospective observational study of patients being tested for the anti-PF4/heparin antibody at our institution from December 2008 to May 2010 using the IgG-specific anti-PF4/heparin ELISA with a two-step assay using high dose heparin in the second step to demonstrate heparin specificity. A positive test was defined as optical density (OD) >0.4 with >50% inhibition. RESULTS: 319 patients were tested during the study period. 23 (7.2%) patients were diagnosed with HIT based on clinical findings (4T score) and ELISA. 16/23 (70%) had thrombosis at diagnosis whereas 7/ 23 (30%) had isolated HIT. All 7 patients with isolated HIT had follow up data for at least 3 months after diagnosis. Only 2/7 were treated with direct thrombin inhibitors (DTI) and 4/7 were treated with warfarin for at least 1 month. While only 3 of the 7 isolated HIT patients had compression ultrasonography to rule out occult lower extremity thrombus, none of these 7 patients (including 4 with an OD of >1.0) developed symptoms or signs of thrombosis in the subsequent 3 months after the diagnosis of isolated HIT. CONCLUSION: The incidence of isolate HIT in this study (7.2%) is significantly lower than previously reported by others and our own historical patients (57.4%, Altuntus et al, Euro J of Haematology 2008) using the IgG, M, A poly -specific anti-PF4/heparin ELISA (z value 2.092, p=0.036). It is possible that many patients previously thought to have HIT by the poly-specific anti-PF4/heparin ELISA assay were false positive. Using the IgG-specific anti-PF4/heparin ELISA not only improved the specificity of the ELISA assay, it also reduced the number of patients with isolated HIT significantly who also seem to have lower risk of developing subsequent thrombosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals To Clot or Not to Clot? Ad is the Question - Insights on Mechanisms Related to Vaccine Induced Thrombotic Thrombocytopenia

2021 ◽  
Author(s):  
Maha Othman ◽  
Alexander T. Baker ◽  
Elena Gupalo ◽  
Abdelrahman Elsebaie ◽  
Carly M. Bliss ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Severe Thrombocytopenia ◽  
Host Proteins ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Autoimmune Condition ◽  
Global Concern ◽  
Mechanistic Basis ◽  
The Uk

Vaccine-induced immune thrombotic thrombocytopenia (VITT), or thrombotic thrombocytopenic syndrome (TTS), has caused global concern. VITT is characterized by thrombosis and thrombocytopenia following COVID-19 vaccinations with the AstraZeneca ChAdOx1 nCov-19 and the Janssen Ad26.COV2.S vaccines. The clinical features of VITT include thrombosis, typically cerebral venous thrombosis, and severe thrombocytopenia developing 5 to 24 days following first dose of vaccine, with elevated D-dimer, and antibodies specific to platelet factor 4 (PF4), signifying platelet activation. As of June 1, 2021, over 1.93 billion COVID-19 vaccine doses had been administered worldwide. Currently, 467 VITT cases (0.000024%) have been reported across the UK, Europe, Canada and Australia. Clinically, VITT presents similarly to a rare autoimmune condition called “spontaneous/autoimmune heparin Induced Thrombocytopenia” (HIT) without prior heparin exposure. Guidance on diagnosis and management of VITT has been reported but the pathogenic mechanism of VITT is not fully elucidated. A definite causal relationship with the vaccine material is yet to be confirmed. To date, it is established that IgG antibodies recognizing PF4 activate platelets through FcγRIIA, however it remains unclear what triggers production of these antibodies. The fact that VITT, has only been described in association with adenoviral vector-based DNA virus vaccines, but not mRNA/lipid-based vaccines, raises the likelihood that the syndrome is somehow linked to the vector or other constituents in the vaccine preparation. Here, we propose and discuss potential mechanisms in relation to adenovirus induction of VITT. We discuss adenovirus immunogenicity and interactions with platelets and other host proteins, the role of PF4 and platelet activation. Whilst confirming a single mechanism underpinning VITT is challenging, we provide insights and clues into areas warranting investigation into the mechanistic basis of VITT, highlighting the unanswered questions. Further research is required to help solidify a pathogenic model for this condition.

scholarly journals Drug-Immune Thrombocytopenia with Thrombosis versus Heparin-Induced Thrombocytopenia: A Critical Clinical Controversy

2015 ◽  
Vol 5 (2) ◽  
pp. 152-159
Author(s):  
Hassan Al-Jafar ◽  
Anas Al-Yousef ◽  
Somaya Al-Shatti ◽  
Khalifa Al-Banwan
Keyword(s):  
Immune Thrombocytopenia ◽  
Recurrent Infection ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Clinical Issue ◽  
Heparin Induced Thrombocytopenia ◽  
Vein Thrombosis ◽  
Below The Knee ◽  
Febrile Episodes ◽  
End Stage

Heparin-induced thrombocytopenia (HIT) is a type of drug-induced immune thrombocytopenia (DITP). DITP is a rare and challenging clinical issue, especially when it is associated with thrombosis. A 62-year-old woman was admitted to our institution with end-stage renal failure. She received heparin for hemodialysis. Six days later, she became febrile and was treated with vancomycin and amikacin antibiotics. Two days after starting the vancomycin, she developed severe thrombocytopenia with extensive gangrenous deep vein thrombosis in her right leg, which required a below-the-knee amputation. The HIT test yielded positive results when heparin was already stopped, but her platelet count did not regenerate even after 3 months of heparin-free treatment. Courses of vancomycin treatment were given during several febrile episodes over the long period of severe thrombocytopenia. The patient was given both anti-immune thrombocytopenia and anticoagulant treatments because of both severe persistent thrombocytopenia and recurrent thrombotic episodes. The patient died as a result of severe thrombocytopenia, recurrent infection, and blood loss from the amputation site. Vancomycin is known to cause DITP, thrombosis, and immune complexes. DITP is a bleeding disorder, whereas HIT is a controversial thrombotic disorder. HIT tests can be influenced by cross-reacting antibodies and many other factors. Thus, there is no single method that can be considered 100% effective in confirming the HIT diagnosis. Anticoagulants must be used with great caution in patients with suspected DITP. Treatment of HIT-positive cases requires both clinical correlation and experience rather than reliance on HIT tests alone.

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