About TTP

Thrombotic Thrombocytopenic Purpura (TTP) is an ultra-rare, acute, and life-threatening blood disorder that causes small clots in blood vessels throughout the body.^viii Normally, platelets (blood cells) float in the blood and form clots only to stop a bleeding.^ix In patients with TTP, platelets form clots when they’re not supposed to, making it hard for blood to move through the blood vessel and get to the rest of the body.^x There are 2 types of TTP: congenital (cTTP) and immune-mediated (aquired) (iTTP).^xi

Congenital TTP - cTTP	Immune-mediated (acquired) TTP - iTTP
Congenital TTP (cTTP) is caused by a problem in a gene that results in low levels of ADAMTS13 in the blood.^xii	Immune-mediated or acquired TTP (iTTP) is caused by a problem in the immune system that results in low levels of ADAMTS13 in the blood.^xiii
cTTP has a prevalence of 0.5-2 cases per million people,^xiv often presents in childhood prior to 10 years of age.	iTTP is the most common form of TTP and often develops during adulthood (90% of all TTP cases) or, more rarely, during childhood (10% of all TTP cases).^xv

Prevalence

TTP is a rare condition, with an annual incidence (new cases) of 3 to 11 cases per million people and a prevalence (total cases – both new and pre-existing) of 10 cases per million people.^xvi

The first acute episode occurs in adulthood in approximately 90% of cases and less frequently during childhood.^xvii

Deficiency in ADAMTS13 enzyme is related to a mutation occurring is both alleles (maternal and paternal) of the ADAMTS13 gene in cTTP (5% of all TTP cases) or to the presence of autoantibodies against ADAMTS13 in immune-mediated TTP (95% of all TTP cases).^xviii

TTP patients can experience multiple relapses, even after many years of follow-up: after 10 years, 36% of patients can experience ≥1 episode.^xix Even when treated, the mortality rounds from 10% to 20%.^xx

Symptoms

Acute TTP events are life-threatening emergencies caused by blood clots, a low platelet count, and damaged red blood cells, and causes a myriad of symptoms, including:^xxi

Diagnosis

Clinical
presentation

Analysis of
medical and
family history

Physical
exams

Test

Urinalysis and renal function tests
Complete blood count (CBC)
Peripheral blood smear
Reticulocyte count
Serum LDH
Haptoglobin
ADAMTS13 activity
Autoantibody assays, serum bilirubin, and direct antiglobulin test ^{xxii, xxiii}

Disease management and treatment

A timely diagnosis and treatment of TTP are crucial for the patient to avoid acute disseminated microthrombosis and irreversible organ damage and death.^xxiv Currently, therapies for the treatment and management of TTP target the ADAMTS13 enzyme, the immune cells involved in anti-ADAMTS13 autoantibodies production, and the interaction between vWF and platelets.^xxv

Burden of disease

TTP has both short and long-term consequences. When untreated, acute mortality rates can reach 90%^xxvi with the majority of deaths occurring within 2 weeks of diagnosis.^xxvii Cardiovascular complications, including stroke, heart failure, and acute coronary syndrome are common and in-hospital mortality is significantly higher in these patients.^xxviii

The management of acute thromboembolism, encompassing conditions like stroke, acute myocardial infarction, or transient ischemic attack, demands a considerable allocation of healthcare resources. This entails hospitalisation for diagnostic procedures, the administration of thrombolytic agents and other pharmaceutical treatments, potential admission to intensive care or critical care units, and the provision of specialised nursing care. These interventions carry a substantial financial strain on the healthcare system ^{xxix, xxx, xxxi} Moreover, rates of depression and cognitive deficits are considerably higher in TTP patients.^xxxii

Recovery following an acute episode of iTTP is not a resolution of symptoms but the beginning of a long-term morbidity burden: hypertension, Systemic Lupus Erythematosus, and depression were significantly greater for TTP survivors.^xxxiii

As patients who survive an acute episode of TTP are at risk of relapse and long-term morbidity, experts call for TTP to be seen and considered as a chronic disease with acute episodes.^xxxiv