scholarly journals Autoimmune- and complement-mediated hematologic condition recrudescence following SARS-CoV-2 vaccination

2021 ◽  
Vol 5 (13) ◽  
pp. 2794-2798
Author(s):  
Andrew Jay Portuguese ◽  
Cassandra Sunga ◽  
Rebecca Kruse-Jarres ◽  
Terry Gernsheimer ◽  
Janis Abkowitz

Abstract A variety of autoimmune disorders have been reported after viral illnesses and specific vaccinations. Cases of de novo immune thrombocytopenia (ITP) have been reported after SARS-CoV-2 vaccination, although its effect on preexisting ITP has not been well characterized. In addition, although COVID-19 has been associated with complement dysregulation, the effect of SARS-CoV-2 vaccination on preexisting complementopathies is poorly understood. We sought to better understand SARS-CoV-2 vaccine-induced recurrence of autoimmune- and complement-mediated hematologic conditions. Three illustrative cases were identified at the University of Washington Medical Center and the Seattle Cancer Care Alliance from January through March 2021. We describe the recrudescence of 2 autoimmune conditions (ITP and acquired von Willebrand Disease [AvWD]/acquired hemophilia A) and 1 complementopathy (paroxysmal nocturnal hemoglobinuria [PNH]). We report the first known case of AvWD/acquired hemophilia A, and describe the first PNH exacerbation in the absence of complement inhibition after SARS-CoV-2 vaccination. Although SARS-CoV-2 vaccine-induced ITP is a known concern, our case clearly depicts how thrombocytopenia in the setting of preexisting ITP can sequentially worsen with each vaccine dose. Based on our experiences and these examples, we provide considerations for how to monitor and assess risk in patients with underlying autoimmune- and complement-mediated hematologic conditions.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1128-1128
Author(s):  
Carolyne Elbaz ◽  
Katerina Pavenski ◽  
Hina Chaudhry ◽  
Jerome M. Teitel ◽  
Michelle Sholzberg

Background Patients with severe congenital hemophilia A (CHA) have a 25-40% lifetime risk of alloantibody (inhibitor) development to FVIII. Patients with acquired hemophilia A (AHA) spontaneously develop neutralizing autoantibodies to factor VIII. In both cases, patients require pro-hemostatic therapy with bypassing agents: recombinant factor VIIa (rFVIIa), activated prothrombin complex concentrate (aPCC) and more recently recombinant porcine factor VIII (rpFVIII). Anti-human FVIII (hFVIII) inhibitors typically bind to the A2 and C2 domains of the FVIII molecule. RpFVIII is an effective pro-hemostatic treatment for AHA and CHA given the immunologic difference in the A2 and C2 domains of the rpFVIII while maintaining sufficient hFVIII homology to act as an effective cofactor to human FIX in the intrinsic tenase. However, some anti-hFVIII antibodies cross-react with rpFVIII and may interfere with its hemostatic function. Cross-reacting antibodies were reported in 35% of subjects in a phase II/III trial prior to initiation of rpFVIII. Moreover, de novo rpFVIII inhibitors may develop during or after the treatment with rpFVIII and may affect its hemostatic function. Here we describe the largest case series to date on baseline cross-reactivity of rpFVIII inhibitors and post-treatment de novo inhibitor development in patients with CHA and AHA to address the paucity of published literature in this area. Aim First, we describe the frequency of baseline cross-reacting rpFVIII inhibitors in patients with AHA and CHA (with inhibitors) at our institution. Second, we describe the effect of baseline rpFVIII antibodies on FVIII recovery after treatment with rpFVIII. We also describe the frequency and timing of de novo rpFVIII inhibitor development after exposure to rpFVIII. Methods Institutional research ethics board approval was obtained. Electronic charts of patients admitted to our institution with AHA or CHA who underwent testing for rpFVIII inhibitors were reviewed retrospectively. RpFVIII inhibitor assay is performed in the special coagulation laboratory using the Nijmegen modified Bethesda assay. The patient sample is initially heat-treated at 57 Results Twenty-seven patients (7 CHA, 20 AHA) underwent testing for porcine inhibitors since assay availability in 2016. 61% (5/7 CHA, 11/20 AHA) of patients had a detectable rpFVIII inhibitor prior to exposure to rpFVIII; median titer 1.6 BU/ml (range 0.6-192). Eight patients with AHA with baseline cross-reacting inhibitors received rpFVIII. Of those, three achieved an initial FVIII recovery beyond 100% (132%, 148% and 177%) after approximately 100U/kg of rpFVIII and all three had very low anti-rpFVIII Bethesda titers (0.70, 0.85 and 0.9 BU/ml). Five patients did not achieve a FVIII recovery above 50% (46%, 46%, 40%, 36% and 0%) despite approximately 100U/kg of rpFVIII. Most patients who received rpFVIII were tested weekly for the duration of their treatment or hospital stay. Upon discharge, patients who were seen in clinic for follow up were tested for anti-hFVIII and anti-rpFVIII. Two AHA patients without a baseline inhibitor who received rpFVIII treatment developed a de novo inhibitor after 20 days (1 BU/ml) and 133 days (12 BU/ml), respectively. One AHA patient had a rise in baseline anti-rpFVIII titer after exposure to rpFVIII. Conclusion In conclusion, we found that 61% of patients with AHA and CHA tested for rpFVIII inhibitors had a detectable baseline cross-reacting inhibitor which is higher than previously described. Of those patients with a baseline inhibitor treated with rpFVIII, only 37.5% of patients had an appropriate rise in FVIII. Finally, 13% of patients without baseline inhibitors developed a de novo inhibitor after exposure to rpFVIII, an incidence comparable to previously published findings. Disclosures Pavenski: Bioverativ: Research Funding; Alexion: Honoraria, Research Funding; Octapharma: Research Funding; Shire: Honoraria; Ablynx: Honoraria, Research Funding. Teitel:BioMarin: Consultancy; CSL Behring: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Shire: Consultancy; Pfizer: Consultancy, Research Funding; Bayer: Consultancy, Research Funding. Sholzberg:Takeda: Honoraria, Research Funding; Baxter: Honoraria, Research Funding; Baxalta: Honoraria, Research Funding. OffLabel Disclosure: Recombinant porcine factor VIII is used to treated patients with congenital hemophilia A with allo inhibitors


2014 ◽  
Vol 3 (1) ◽  
pp. 21 ◽  
Author(s):  
Christina Dicke ◽  
Katharina Holstein ◽  
Sonja Schneppenheim ◽  
Rita Dittmer ◽  
Reinhard Schneppenheim ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4212-4212
Author(s):  
Manpreet K. Sandhu ◽  
Trishala Agrawal ◽  
Maya Shah ◽  
Alice J. Cohen

Abstract Abstract 4212 Background: Literature has revealed that there is considerable inappropriate use of blood products including cryoprecipitate (cryo). Appropriate indications for cryo use according to American Association of Blood Banks (AABB) guidelines include bleeding due to hypofibrinogenemia (fibrinogen level < 100mg/dl) or dysfibrinogenemia, factor XIII deficiency, bleeding associated with Hemophilia A or von Willebrand disease (when appropriate factor concentrates are not available) and uremic bleeding (DDAVP preferred). To determine appropriateness of use of cryo at Newark Beth Israel Medical Center, a review of cryo utilization was conducted at this tertiary care hospital. Methods: A retrospective audit of cryo utilization was performed from January to May 2011. Medical records of all patients (pts) who received cryo during this time were reviewed for demographic information (age, sex, clinical diagnosis) and relevant laboratory data (PT, PTT, fibrinogen levels, serum creatinine). The number of units transfused per pt as well as the hospital service requesting the transfusion in each case was noted. The indication of cryo in each case was evaluated as appropriate or inappropriate, depending on AABB transfusion guidelines. Results: A total of 62 pts received 71 pooled cryo transfusions (total of 691 units). Out of the 71 transfusions, 61 in 52 pts (585 units) were evaluable with complete data. Mean age of these pts was 53 years (yrs) (range 0–83), with 42% being females. Mean number of units given per transfusion was 9.7(range 1–20). The majority of cryo use was by cardiothoracic (CT) surgery (360/585, 62%) followed by hematology/oncology (hem/onc) (177/585, 30%). The remainder was used by Pediatrics (Peds) (23/585, 4%) and Obstetrics/Gynecology (Ob/Gyn) (25/585, 4%). All the transfusions were given in the setting of bleeding. The most common reason for transfusion (201/585, 34%) was post-operative bleeding, without any clear indication based on guidelines, and predominantly ordered by CT surgery (165/201, 82%). 180/585 (31%) of the units were transfused intraoperatively with 160/180 (89%) of those transfusions occurring during cardio-thoracic procedure. In 8 pts, 81 cryo units (81/585, 14%) were transfused to correct uremic bleeding, and were all ordered by hem/onc. 12 pts received 93 units (93/585, 16%) for bleeding related to hypofibrinogenemia. 11/12 of these pts had disseminated intravascular coagulation (DIC), with 1/11 cases of DIC due to underlying malignancy, 9/11 due to sepsis and 1/11 due to acute fatty liver of pregnancy. Overall, 174/585 (30%) of cryo units were transfused appropriately as per AABB guidelines: 93/174(53%) for hypofibrinogenemia and 81/174 (47%) for uremic bleeding. The highest incidence of cryo transfusions for appropriate indications was in the hem/onc department (131/174, 75%). The total cost of inappropriate transfusions was $23,838 (411/585 units, calculated using $58 per unit). Of note, none of the cryo transfusions were used for bleeding Hemophilia A or von Willebrand disease pts since our medical center uses recombinant factor for those indications. Conclusions: Cryo utilization varied by departments. CT surgery followed by hem/onc services are the principal users of cryo in our tertiary care hospital. As only 30% of cryo was used in accordance with established guidelines, the opportunities may exist for lower cryo usage. Further education of the medical community is warranted regarding the appropriate clinical indications for the use of cryo, in order to decrease the risks with transfusion (such as transmission of infectious agents) as well as to save the cost of unnecessarily transfused blood products. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 8 ◽  
pp. 2050313X2090674
Author(s):  
Akeem Lewis ◽  
Joe Joseph ◽  
Nirmal Pathak ◽  
Babak Baseri ◽  
Carol Luhrs

Acquired hemophilia A or acquired factor VIII deficiency is a rare bleeding disorder due to the presence of autoantibodies to factor VIII. It has been associated with autoimmune conditions, certain medications, and malignancy. It has a high morbidity and mortality, and early diagnosis and treatment is critically important. Acquired hemophilia A usually manifests with soft tissue bleeding, such as epistaxis, genitourinary, or gastrointestinal bleeding and rarely with hemarthrosis. In this case report, we present the management of an uncommon case of acquired hemophilia A in a patient with metastatic prostate adenocarcinoma who presented with both hemarthrosis and soft tissue bleeding. Bleeding was controlled with recombinant factor VIIa, factor VIII bypassing agent, and immunosuppressive therapy with prednisone and rituximab. Chemotherapy with docetaxel was also promptly initiated to address the underlying condition and achieve long-term remission, which is currently ongoing for 10 months.


Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3378-3384 ◽  
Author(s):  
PJ van Genderen ◽  
T Vink ◽  
JJ Michiels ◽  
MB van 't Veer ◽  
JJ Sixma ◽  
...  

Abstract An 82-year-old man with a low-grade malignant non-Hodgkin lymphoma and an IgG3 lambda monoclonal gammopathy presented a recently acquired bleeding tendency, characterized by recurrent epistaxis, easy bruising, and episodes of melena, requiring packed red blood cell transfusions. Coagulation studies showed a von Willebrand factor (vWF) defect (Ivy bleeding time, > 15 minutes; vWF antigen [vWF:Ag], 0.08 U/mL; ristocetin cofactor activity [vWF:RCoF], < 0.05 U/mL; collagen binding activity [vWF:CBA], 0.01 U/mL; absence of the high molecular weight multimers of vWF on multimeric analysis). Mixing experiments suggested the presence of an inhibitor directed against the vWF:CBA activity of vWF without significantly inhibiting the FVIII:C, vWF:Ag, and vWF:RCoF activities. The inhibitor was identified as an antibody of the IgM class by immunoabsorption of vWF and inhibitor-vWF complexes from the plasma of the patient. Subsequent immunoprecipitation experiments using recombinant fragments of vWF showed that the inhibitor reacted with both the glycoprotein Ib binding domain (amino acids [aa] 422–826) and the A3 (aa 909–1112) domain of vWF, but not with the A2 (aa 716–908) or D4 (aa 1183–1535) domains. We conclude that the IgM autoantibody inhibits the vWF:CBA activity by reacting with an epitope present on both the glycoprotein Ib and A3 domains of vWF.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Quentin Binet ◽  
Catherine Lambert ◽  
Laurine Sacré ◽  
Stéphane Eeckhoudt ◽  
Cedric Hermans

Background. Acquired hemophilia A (AHA) is a rare condition, due to the spontaneous formation of neutralizing antibodies against endogenous factor VIII. About half the cases are associated with pregnancy, postpartum, autoimmune diseases, malignancies, or adverse drug reactions. Symptoms include severe and unexpected bleeding that may prove life-threatening.Case Study. We report a case of AHA associated with bullous pemphigoid (BP), a chronic, autoimmune, subepidermal, blistering skin disease. To our knowledge, this is the 25th documented case of such an association. Following treatment for less than 3 months consisting of methylprednisolone at decreasing dose levels along with four courses of rituximab (monoclonal antibody directed against the CD20 protein), AHA was completely cured and BP well-controlled.Conclusions. This report illustrates a rare association of AHA and BP, supporting the possibility of eradicating the inhibitor with a well-conducted short-term treatment.


2013 ◽  
Vol 46 (4) ◽  
pp. 135-139
Author(s):  
Chia-Wei Chang ◽  
Jiun-Ting Yeh ◽  
Shang-Yu Wang ◽  
Chun-Hsiang Ouyang ◽  
Chien-Hung Liao ◽  
...  

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