Get to know thrombotic thrombocytopenic purpura in five minutes

Thrombotic thrombocytopenic purpura (TTP) is a disseminated thrombotic microangiopathy clinically characterized by the classic quintuad: i.
e.
, thrombocytopenia, microangiopathic hemolytic anemia, variable neurologic symptoms and signs, renal impairment, and fever
.
The disease is more common in adults around 30~40 years old, female: male is 2:1
.
Hemolytic uremic syndromes (HUS) are also a type of
thrombotic microangiopathy.
Adult thrombotic microangiopathy with obvious neurological symptoms is often referred to clinically as TTP; Child-type vascular microangiopathy with predominantly renal damage is called HUS
.


【Clinical manifestations】The clinical manifestations of classic TTP include the five signs of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms and signs, renal damage, and fever
.
Analysis of a group of 258 TTP cases from Ridolfi and Bell showed that only 40% of patients had pentadoptyl; 74% of patients have anemia, thrombocytopenia, and neurological symptoms (triad).

In addition to the above symptoms, patients may have non-specific symptoms such as malaise, weakness
.
Neurologic symptoms and bleeding symptoms are the most common complaints
.
Neurologic symptoms include headache, cranial nerve palsy, loss of positional awareness, aphasia, paresis, confusion, stupor, coma, and convulsions
.
Cutaneous purpura and retinal hemorrhage are the most common sites of bleeding and can also present with gastrointestinal and genitourinary bleeding
.
50% of patients have fever
.
Renal manifestations include proteinuria, hematuria, and mild renal impairment
.
Other manifestations such as cardiac conduction abnormalities, myocardial infarction, pancreatic inflammatory abdominal pain, etc.
; Intestinal wall infarction may also occur, but the incidence is low
.
【Diagnosis and differential diagnosis】TTP diagnosis is mainly based on the clinical characteristic "pentad"
.
The minimum criteria for the diagnosis of TTP are thrombocytopenia without obvious clinical etiology and microangiopathic haemolytic anaemia
.
Patients have neuropsychiatric symptoms and signs, as well as varying degrees of renal impairment
.
Peripheral blood smear showing red blood cell disruption is important but not necessary for diagnosis, as red blood cell disruption on the blood smear is not a constant feature of
TTP.
Elevated serum LDH levels are a valid indicator
of haemolysis.
Differential diagnosis should include: (1) HUS: HUS is a localized microangiopathy that mainly involves the kidneys, and children have a high incidence and often have a history of infection before the onset, especially E.
coli 0157:H7 strain infection
.
The disease mainly affects the kidneys, such as oliguria, hypertension, severe renal damage, and neurological symptoms are rare
.
(2) Gestational hypertension syndrome: In pregnancy-induced hypertension syndrome pre-eclampsia or eclampsia, patients can have many symptoms similar to TTP, but the prognosis of the disease is relatively good, and the onset may be related to
mild intravascular coagulation.
(3) Active systemic lupus erythematosus with immune thrombocytopenia and vasculitis
.
(4) Severe idiopathic thrombocytopenic purpura with autoimmune hemolytic anemia
.
(5) Paroxysmal nocturnal hemoglobinuria
.
【Treatment】Before the 70s, without plasma exchange and plasma transfusion therapy, the mortality rate of TTP was about 90%, most of which died within 3 months after the onset, and 10% of patients survived less than 1 year
.
At present, with the application of plasma exchange technology, more than 80% of patients can survive
.
Therefore, once TTP is confirmed, the treatment of choice is plasma exchange, which is at least one plasma volume per day until platelet count returns to normal
.
Serum LDH levels may or may not return to normal levels, and it usually takes 10 days or more
to achieve this goal.
Mechanisms of plasma exchange therapy for TTP may include: (1) removal of abnormal vWF polymers; Platelet aggregation factor and circulating immune complex.

(2) The "processing" factor or PGI2
of large molecular weight vWF is supplemented.
Before plasma exchange, or without conditions for plasma exchange, fresh cryopreserved plasma, or supernatant fractions of plasma
precipitates, can be transfused.
Other treatments include glucocorticoids, antiplatelet drugs, vincristine, intravenous immunoglobulin, PGI2 use, and even splenectomy, and the efficacy of these therapies is uncertain
.
In the treatment of TTP, platelet
transfusions should be avoided.
Because platelet transfusion can aggravate neurological symptoms and renal impairment
in TTP patients.
【Prognosis】Before the introduction of plasma exchange therapy, the mortality rate of TTP patients reached 90%.

Even with plasma exchange therapy, the reported mortality rate is still 15%~30%.

Mortality is relatively high
in older patients with TTP.
Patients who achieve clinical remission of TTP after treatment still have the possibility of recurrence within 10 years, and the recurrence rate of TTP within 10 years has been reported to be about 36%, but the mortality rate of recurrent TTP is significantly lower than that of the first case
.