Guidelines Overview Chinese Guidelines for the Diagnosis and Treatment of Thrombocytopenic Purpura (2022 Edition) (1)

Thrombotic thrombocytopenic purpura (TTP) is a rare and severe thrombotic microangiopathy whose main clinical features include microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neuropsychiatric symptoms, fever, and renal failure.
Tired
etc.

The pathogenesis of TTP mainly involves the lack of von Willebrand factor (VWF) lyase (ADAMTS13) activity, and is also associated with the abnormal release of VWF from vascular endothelial cells, the abnormal activation of complement, and the abnormal activation of platelets
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Lack of ADAMTS13 activity in plasma leads to abnormal release of ultramolecular VWF (UL-VWF) from endothelial cells that cannot be degraded in time.
UL-VWF can spontaneously bind to platelets, leading to thrombosis in microvascular and microangiopathic hemolysis, which in turn causes ischemia and ischemia of corresponding organs.
Oxygen and dysfunction, causing clinical syndromes
.

According to the different mechanisms of ADAMTS13 deficiency, TTP is divided into hereditary TTP (cTTP, also known as Upshaw-Schulman syndrome) and immune TTP (iTTP)
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The mutation of cTTP-based ADAMTS13 gene leads to the lack of plasma ADAMTS13 activity, which is often caused by precipitating factors such as infection, inflammation or pregnancy
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cTTP is inherited in an autosomal recessive manner, and the gene mutation is either homozygous or double heterozygous
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iTTP accelerates the clearance of ADAMTS13 in vivo due to the production of anti-ADAMTS13 autoantibodies in patients, inhibiting ADAMTS13 activity (neutralizing antibody) or combining with ADAMTS13 to form an antigen-antibody complex
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Most iTTPs have no clear cause (ie, primary), and may also be secondary to infections, drugs, tumors, autoimmune diseases, and hematopoietic stem cell transplantation
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iTTP is the most common clinical type, accounting for about 95% of the total cases of TTP; cTTP is relatively rare, accounting for only 5% of the total cases, but cTTP accounts for 25% to 50% in children and pregnant patients
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The Thrombosis and Hemostasis Group of the Chinese Society of Hematology has formulated the "Chinese Guidelines for the Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura (2022 Edition)"
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Today, the editor will organize the clinical manifestations, laboratory examinations and clinical diagnosis related content as follows for readers' reference
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01Clinical manifestations Foreign data show that the annual incidence of TTP is 2-6/million, the ratio of women to men is about 2:1, and the peak age of onset is 30-50 years old, but some cTTP patients can develop the disease in the neonatal period.
Most patients with TTP have abrupt onset and are in critical condition, while a few patients have insidious onset and atypical clinical manifestations.
Inflammation, infection, pregnancy, etc.
are common causes of TTP, and female patients with cTTP often have disease attacks in early pregnancy
.

The typical clinical manifestations of TTP are as follows: ① Hemorrhage: mainly skin and mucous membranes, severe cases may have visceral or intracranial hemorrhage
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② MAHA: mostly mild to moderate anemia, may be accompanied by jaundice
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③ Neuropsychiatric symptoms: manifested as confusion of consciousness, headache, aphasia, convulsions, visual disturbances, delirium, hemiplegia, and focal sensory or motor disturbances
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④ Kidney damage: proteinuria, hematuria, cast urine, slightly elevated blood urea nitrogen and creatinine may occur
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⑤ Fever (>37.
5 ℃)
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⑥Clinical manifestations of other organ damage such as chest pain, abdominal pain, fatigue, arthralgia, muscle pain,
etc.

Clinically, patients who completely conform to the typical "pentad" of TTP are relatively rare, and the "triad" with MAHA, thrombocytopenia and neuropsychiatric symptoms is more common.

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Since some TTP patients have insignificant neuropsychiatric symptoms, it is recommended that if MAHA and thrombocytopenia are found, they should be highly alert to the possibility of TTP, and conduct relevant laboratory tests and comprehensive clinical evaluations in a timely manner
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02 Laboratory blood routine examination and blood smear examination showed different degrees of anemia.
The peripheral blood smear showed broken red blood cells (>1%), and the proportion of reticulocytes was mostly increased; the platelet count was significantly decreased (mostly lower than 20×109/L).
And the dynamic decline is more significant
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Blood biochemical examinations mainly include increased blood bilirubin, mainly indirect bilirubin; serum lactate dehydrogenase (LDH) was significantly increased; blood urea nitrogen and creatinine increased to varying degrees, and the level of troponin T increased High in myocardial damage
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Plasma ADAMTS13 activity and inhibitor or IgG antibody determination At present, FRET-VWF fluorescent substrate assay, residual collagen binding assay or immunological ELISA method is used to measure ADAMTS13 activity, ADAMTS13 inhibitor or IgG antibody
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Plasma ADAMTS13 activity was significantly reduced (<10%) in TTP patients; ADAMTS13 activity was significantly reduced in iTTP patients and ADAMTS13 inhibitor or IgG antibody was detected; cTTP patients did not have ADAMTS13 inhibitor or IgG antibody, and gene sequencing was helpful for differential diagnosis
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Plasma ADAMTS13 activity and inhibitor or IgG antibody determination Blood samples should be collected before plasma exchange as much as possible, and attention should be paid to hyperbilirubinemia, hyperlipidemia, elevated free hemoglobin, and plasma proteases that may interfere with the detection of plasma ADAMTS13 activity.
Pay attention to the results
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Coagulation examination activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen detection were mostly normal, occasionally slightly increased fibrin degradation products
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Hemolysis-related tests showed that the direct anti-human globulin test of red blood cells was negative, but positive in some patients with secondary immune diseases; plasma free hemoglobin increased and serum haptoglobin decreased
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ADAMTS13 gene detection For patients suspected of cTTP, ADAMTS13 gene mutation detection can be used to help establish diagnosis and genetic counseling
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Other hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) virus serological examination, thyroid function, antinuclear antibody spectrum, lupus anticoagulant, antiphospholipid antibody, brain CT, Magnetic Resonance Imaging (MRI) and EEG
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03 Clinical diagnosis With TTP clinical manifestations are often MAHA and thrombocytopenia.
Not all patients have the so-called "triad" or "pentad".
Clinically, it is necessary to carefully analyze the condition and find the cause
.

Typical blood cell changes and blood biochemical changes are anemia, platelet count is significantly reduced, especially red blood cell fragments in peripheral blood smears > 1%; serum free hemoglobin is increased, and serum lactate dehydrogenase is significantly increased
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Plasma ADAMTS13 activity was significantly reduced (<10%) iTTP was often detected ADAMTS13 inhibitor or IgG antibody
.

Hemolytic uremic syndrome (HUS), disseminated intravascular coagulation (DIC), HELLP syndrome, Evans syndrome, eclampsia, catastrophic antiphospholipid antibody syndrome and other diseases were excluded
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The diagnosis of patients with typical clinical manifestations is not difficult, but there are obvious individual differences in the clinical manifestations of most patients, and the clinical manifestations of some patients are not characteristic
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Clinical data should be comprehensively collected for newly diagnosed patients, and the risk of TTP should be assessed for suspected patients.
The PLASMIC scoring system is recommended (Table 1): a score of 0 to 4 is considered low risk, and the TTP prediction efficiency is <
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The clinical verification found that the sensitivity and specificity of diagnosing TTP were 81.
7% and 71.
4% in high-risk patients
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Table 1 PLASMIC score for assessing the risk of thrombotic thrombocytopenic purpura (TTP) For patients with moderate or high suspicion of TTP clinical assessment, blood samples should be collected and sent for ADAMTS13 activity and inhibitor or IgG antibody determination.
Plasma exchange and glucocorticoid therapy can be initiated without waiting for test results to be reported
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If the follow-up test reports that the plasma ADAMTS13 activity is less than 10% of the normal mixed plasma activity, TTP can be diagnosed; if the plasma ADAMTS13 activity is more than 20%, TTP can be basically ruled out; the plasma ADAMTS13 activity of 10% to 20% cannot completely rule out TTP, and it needs to be based on clinical judgment.
and close follow-up
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The TTP diagnosis process is shown in Figure 1
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Figure 1 Flow chart of diagnosis of thrombotic thrombocytopenic purpura (TTP) // To be continued In the next issue of the "Chinese Guidelines for the Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura (2022 Edition) (2)", we will continue to share the guidelines Please look forward to the relevant content of TTP treatment and prevention in China! This article is excerpted from the Thrombosis and Hemostasis Group of the Chinese Society of Hematology.
Chinese Guidelines for the Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura (2022 Edition) [J] .
Chinese Journal of Hematology, 2022, 43(1) : 7-12.
DOI : 10.
3760/cma.
j.
issn.
0253-2727.
2022.
01.
002.
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