Recent advances in the management of immune-mediated thrombotic thrombocytopenic purpura

Sung Hwa Bae; Sung-Hyun Kim; Soo-Mee Bang

doi:10.5045/br.2022.2022005

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Blood Res 2022; 57(S1):

Published online April 30, 2022

https://doi.org/10.5045/br.2022.2022005

Recent advances in the management of immune-mediated thrombotic thrombocytopenic purpura

Sung Hwa Bae¹, Sung-Hyun Kim², Soo-Mee Bang³

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Department of Internal Medicine, ¹Daegu Catholic University Hospital, Daegu Catholic University School of Medicine, Daegu, ²Dong-A University Hospital, Dong-A University College of Medicine, Busan, ³Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

Correspondence to : Sung Hwa Bae, M.D., Ph.D.
Department of Internal Medicine, Daegu Catholic University Hospital, Daegu Catholic University School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea
E-mail: sunghwa@cu.ac.kr

Received: January 6, 2022; Revised: February 22, 2022; Accepted: February 28, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially life-threatening thrombotic microangiopathy caused by autoantibody-mediated severe ADAMTS13 deficiency. TTP should be suspected in patients with microangiopathic hemolytic anemia and thrombocytopenia without a definite cause. Early detection of iTTP and prompt treatment with plasma exchange and corticosteroids are essential. Rituximab administration should be considered for refractory or relapsed iTTP, and can be used as a first-line adjuvant or preemptive therapy. Treatment with caplacizumab, a novel anti-von Willebrand factor nanobody, resulted in a faster time to platelet count response, significant reduction in iTTP-related deaths, and reduced incidence of refractory iTTP. TTP survivors showed a higher rate of chronic morbidities, including cardiovascular disease and neurocognitive impairment, which can lead to a poor quality of life and higher mortality rate. Meticulous long-term follow-up of TTP survivors is crucial.

Keywords Thrombotic thrombocytopenic purpura, ADAMTS13 protein, Rituximab, Plasma exchange

Article

Review Article

Blood Res 2022; 57(S1): S37-S43

Published online April 30, 2022 https://doi.org/10.5045/br.2022.2022005

Recent advances in the management of immune-mediated thrombotic thrombocytopenic purpura

Sung Hwa Bae¹, Sung-Hyun Kim², Soo-Mee Bang³

Correspondence to:Sung Hwa Bae, M.D., Ph.D.
Department of Internal Medicine, Daegu Catholic University Hospital, Daegu Catholic University School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea
E-mail: sunghwa@cu.ac.kr

Received: January 6, 2022; Revised: February 22, 2022; Accepted: February 28, 2022

Abstract

Keywords: Thrombotic thrombocytopenic purpura, ADAMTS13 protein, Rituximab, Plasma exchange

Abstract

Fig 1.

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Figure 1.Current approach for patients with suspected iTTP in Korea. Plasma exchange (PEX) should be initiated at the earliest when throm-botic thrombocytopenic purpura is suspected. Daily PEX can be discontinued once platelet count is normalized for 2 days. A suboptimal response is defined as a lack of platelet count increment after 5 days of PEX or initial im-provement followed by a decrease in platelet count while receiving PEX. Although rituximab treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) has not been approved in Korea, the off-label use of rituximab should be considered for refractory iTTP. Currently, caplacizumab is unavailable in Korea. *ADAMTS13 gene sequencing should be considered in patients who have no detectable anti-ADAMTS13 antibodies and persistent severe ADAMTS13 deficiency during clinical remission.

Blood Research 2022; 57: S37-S43https://doi.org/10.5045/br.2022.2022005

Table 1 . Thrombotic microangiopathy syndromes..

Primary TMA^a)

TTP

Congenital

Acquired (immune-mediated)

Complement mediated atypical hemolytic uremic syndrome

Congenital

Acquired

Secondary TMA

Shiga toxin producing Escherichia coli hemolytic uremic syndrome

Disseminated intravascular coagulation

Infection associated TMA

Cancer associated TMA

Drug induced TMA

Immune-mediated

Toxic

Transplant associated TMA

Malignant hypertension

Autoimmune disease (e.g., systemic lupus erythematosus, systemic sclerosis, antiphospholipid syndrome) associated TMA

Pregnancy associated TMA

Pre-eclampsia, eclampsia

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)

^a)Precipitating factors, such as infections and pregnancy, may trigger an acute episode of primary thrombotic microangiopathy (TMA). Some patients with transplant-associated or pregnancy- associated TMA have a genetic predisposition..

Table 2 . Clinical scoring systems to estimate the probability of severe ADAMTS13 deficiency in patients with TMA..

	French score	PLASMIC score
Platelet count	≤30×10⁹ L: +1	<30×10⁹ L: +1
Creatinine level	≤2.26 mg/dL: +1	<2.0 mg/dL: +1
Hemolysis variable^a)		+1
No active cancer		+1
No history of solid-organ or stem-cell transplantation		+1
MCV <90 Fl		+1
INR <1.5		+1
ANA	+1
Total score and likelihood of TTP	0: 2%	0–4 (low risk): 0–4%
	1: 70%	5 (intermediate risk): 9–24%
	2–3: 94%	6–7 (high risk): 62–82%

^a)Reticulocyte count >2.5%, undetectable haptoglobin, or indirect bilirubin >2.0 mg/dL. Abbreviations: MCV, mean corpuscular volume; INR, international normalized ratio; ANA, antinuclear antibody..