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Von Willebrand factor (VWF) multimer (MM) pattern in autoimmune thrombotic thrombocytopenic purpura (iTTP) during acute episodes and in remission

1University Medical Center of the Johannes Gutenberg University, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 2Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 3Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium, Kortrijk, West-Vlaanderen, Belgium, 4Laboratory for Thrombosis Research, IRC, KU Leuven Campus Kortrijk, Belgium, Kortrijk, West-Vlaanderen, Belgium, 5Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium., Leuven, Vlaams-Brabant, Belgium, 6Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Mainz, Germany, Mainz, Guatemala, Germany, 7Transfusion Center, University Medical Center of Johannes Gutenberg-University, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 8Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 9Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, mainz, Rheinland-Pfalz, Germany, 10Laboratory for Thrombosis Research, IRC, KU Leuven Campus Kortrijk, Belgium, Leuven, West-Vlaanderen, Belgium, 11University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany

Abstract Number: PB0299

Meeting: ISTH 2022 Congress

Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » ADAMTS13 and TTP

Background: iTTP is caused by autoantibody-mediated severe ADAMTS13 deficiency causing insufficient proteolytic processing of VWF-MM. The (unusually)-large VWF-MM lead to microvascular platelet thrombi and organ ischemia. Elimination of autoantibodies leads to normalization of ADAMTS13 and clinical remission. Recurrence of acute iTTP is associated with reappearance of ADAMTS13 deficiency and ULVWF-MM. Some patients remain in remission despite recurring/persisting severe ADAMTS13 deficiency.

Aims: We repeatedly investigated VWF-MM and ADAMTS13 in iTTP patients at acute episode-onset and in remission over 2 years.

Methods: Total cohort of 78 iTTP patients: 10 suffered from 16 acute iTTP episodes, samples before plasmapheresis were available. For 11 instances a sample was available before the acute iTTP. 68 patients had no acute iTTP during follow-up, 15 with ADAMTS13 < 10%, 53 with ADAMTS13 >10%. A new VWF-MM ratio (HMW/LMW) based on modified evaluation of Sebia electrophoresis gels was compared to ADAMTS13 activity.

Results: VWF ratio was significantly higher (p < 0.0025) in remission with < 10% as compared to remission with >10% ADAMTS13 activity. 16 samples of acute iTTP showed significantly lower VWF ratio despite < 10% ADAMTS13 in 15. Eleven samples obtained 39 days (IQR9-42) before acute iTTP (ADAMTS13 < 10% in 6, 10-26% in 5) had VWF ratios significantly higher than those from 15 patients in continuing remission with ADAMTS13 < 10% (p < 0.05).

Conclusion(s): The VWF ratio is not dependent exclusively on ADAMTS13 activity. ADAMTS13 regulates the size of VWF-MM as evidenced in patients with continuing remission with < 10% vs. >10% ADAMTS13 activity. The disappearance of HMW-VWF-MM in acute iTTP resulting in a low VWF ratio may be explained by consumption of larger VWF-MM in the iTTP process. The very high VWF ratio preceding acute iTTP recurrence with ADAMTS13 between < 10% and 26% suggests that VWF processing is hampered more than in similarly ADAMTS13 deficient patients remaining in remission.

Figure 1

VWF ratio and ADAMTS13 activity in 78 iTTP patients. Ten patients suffered from 16 acute episodes and 68 stayed in clinical remission throughout the follow-up period. The VWF ratio values are shown before and at the beginning of the acute relapse as well as in remission. 68 iTTP patients who were constantly in remission are grouped according to ADAMTS13 values below and above 10%. -*p < 0.05, **p < 0.025, ***p < 0.0025, ****p < 0.0001-

To cite this abstract in AMA style:

Falter T, Roßmann H, Dekimpe C, de Waele L, Roose E, von Auer C, Degreif A, Marandiuc D, Messmer X, Lackner K, de Meyer S, Jurk K, Vanhoorelbeke K, Lämmle B. Von Willebrand factor (VWF) multimer (MM) pattern in autoimmune thrombotic thrombocytopenic purpura (iTTP) during acute episodes and in remission [abstract]. https://abstracts.isth.org/abstract/von-willebrand-factor-vwf-multimer-mm-pattern-in-autoimmune-thrombotic-thrombocytopenic-purpura-ittp-during-acute-episodes-and-in-remission/. Accessed September 21, 2023.

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