How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome

Scully, Marie; Goodship, Tim

doi:10.1111/bjh.12718

Cited by 136 publications

(147 citation statements)

References 43 publications

(44 reference statements)

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“…It carries a high mortality in the event of a missed diagnosis (~90%), [6] but with appropriate management survival is excellent (~80%). [7] Other causes include autoimmune disease, a variety of drugs (including clopidogrel, ticlodipine and quinine) and congenital deficiency of ADAMTS13 (a metalloproteinase that cleaves high molecular weight Von Willebrand factor). HIV remains the most common cause in SA.…”

Section: Fragmentation Haemolysismentioning

confidence: 99%

“…In the developed world, much emphasis is placed on the importance of documenting ADAMTS13 levels in the diagnosis of TTP, where its activity is reportedly consistently low (<10%) in congenital and autoimmune-mediated TTP, but normal or more modestly reduced in other microangiopathies. [7] However, ADAMTS13 levels are not universally low in HIV-associated TTP, which places the use of this test in question in the SA context. [8] Furthermore, ADAMTS13 testing is not universally available in SA, and it is therefore not routinely recommended.…”

Section: Fragmentation Haemolysismentioning

confidence: 99%

See 1 more Smart Citation

Anaemia: Approach to diagnosis (part 2)

2017

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Anaemia is defined as a condition in which the number of red cells or their oxygen-carrying capacity is insufficient to meet physiological needs. It is the most common disorder globally and one of the conditions that general practitioners most frequently encounter. In the World Health Organization global database, anaemia is estimated to affect 1.6 billion people. Anaemia may result from (i) decreased bone marrow output; or (ii) peripheral loss, destruction or sequestration of red cells. As anaemia manifests in a whole range of conditions, it is important to embrace a structured diagnostic approach. The recommended approach incorporates clinical and pathophysiological considerations, red cell characteristics, and bone marrow activity. Causes of anaemia related to decreased bone marrow output have been discussed in the previous issue of SAMJ, in the first part of this two-part series. The focus of the current article is on peripheral causes of anaemia.

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Section: Fragmentation Haemolysismentioning

confidence: 99%

Section: Fragmentation Haemolysismentioning

confidence: 99%

Anaemia: Approach to diagnosis (part 2)

2017

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“…This process is crucial to control VWF activity and maintain equilibrium of haemostasis and thrombosis in plasma. Severely reduced ADAMTS13 activity ( < 5%-10%) results in aggregation of platelets on the ultra-large VWF and widespread microthrombi formation in small arterioles and capillaries throughout the body -the characteristic pathological feature of TTP [4].…”

Section: Thrombotic Thrombocytopenic Purpuramentioning

confidence: 99%

Atypical hemolytic uremic syndrome: from diagnosis to treatment

Franchini¹

2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Thrombotic microangiopathy (TMA) is a relatively rare condition but a medical urgency requiring immediate intervention to avoid irreversible organ damage or death. Symptoms on presentation include microangiopathic haemolytic anaemia, thrombocytopenia and organ damage. The most frequent direct causes of TMA are thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome (HUS). The most common form of HUS is related to Shiga toxin producing Escherichia coli (STEC) infection while approximately 10% of cases are due to dysregulation of the complement pathway (atypical haemolytic uremic syndrome, aHUS). Optimal treatment regimens differ depending on the underlying cause; however, differential diagnosis may be difficult. The most accurate method of diagnosis is based on exclusion and should consider, beyond the symptoms common to TMA, ADAMTS13 activity levels and STEC infection status. For the management of TTP, plasma exchange (PE) is the most important acute intervention and is associated with lower mortality and better outcomes than plasma infusion. In most patients with STEC-HUS, the course of disease is selflimiting although management of acute kidney injury is often required. Until recently, the management of aHUS consisted of early and intensive PE, although this was mostly ineffective in protecting from subsequent organ damage. Eculizumab, an inhibitor of the alternative complement pathway, produces a rapid and sustained inhibition of the TMA process, with significant improvements in long-term clinical outcomes. Due to the significant improvement achieved, eculizumab has subsequently been approved as first-line therapy when an unequivocal diagnosis of aHUS has been made.

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“…Pre-implantation diagnosis should be discussed. Plasma therapy, either with regular infusions of fresh frozen plasma and or PE has been the mainstay of treatment prior to the use of eculizumab (76) and may be helpful especially in patients with no identified complement mutation or in whom TTP is suspected (5). Plasma therapy has reduced the high mortality rate and prevented relapses but is far from optimal.…”

Section: Treatment Of Deap-husmentioning

confidence: 99%

“…Although it is now clear that HUS and thrombotic thrombocytopenic purpura (TTP) are completely different clinico-pathological entities, there are cases, more often in adults than in children that can be difficult to distinguish clinically (4). However, it is important to note that patients with TTP usually have ≤ 5% of normal ADAMTS13 levels (5). HUS may be may be acquired or inherited; some patients have an environmental trigger and a genetic mutation ( Table 1).…”

Section: Introductionmentioning

confidence: 99%