Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS)

Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS)


Hello, I’m Dr. [INAUDIBLE]. And I will talk about Thrombotic Thrombocytopenic Purpura TTP, and hemolytic uremic syndrome, HUS. Thromobotic thrombocytopenic purpura, TTP, has been classically diagnosed with the pentad of microangiopathic hemolytic anemia, which causes a Coombs negative hemolytic anemia. Hemolytic markers such as heptoglobulin will be low, with a raised LDH, bilirubin and erratic oocytes count. The typical blood film seen will be of numerous fragmented cells or cystocytes, with anisopoikilocytosis, polychromecia, and thrombocytopenia. The thrombocytopenia is due to consumption of platelet during the formation of microthrombi. Renal impairment usually present acutely, which may require dialysis support, but usually is not the main presentation or manifestation. Neurological manifestation can have a wide range of presentations, such as headache, connective impairment, blurring of vision, hemiparesis, seizure, and coma, et cetera. Fever– this can be nonspecific, but usually present in most of the patients. Hemolytic uremic syndrome, HUS, usually occurs in children and half the classical clinical presentations of acute renal impairment, which may be the main presentation and may require dialysis support. However, the classical hemolytic uremic syndrome usually runs a self-limiting process, with long term sequelae. Patient also have microangiopathic hemolytic anemia, MAHA, with similar laboratory findings like TTP. The etiology of TTP can be divided into congenital or acquired. There are many etiology for acquired TTP, and these have to be considered when a patient is diagnosed with TTP. The main reason to ascertain the etiology is because responsive treatment is different. HUS is classically divided into typical, associated with diarrhoea, or atypical, not associated with diarrhea. The main difference between these two is that classical HUS has excellent prognosis with supportive treatment and self resolving, while atypical HUS needs plasma exchange, with poor prognosis. We will concentrate more on the classical HUS in this presentation. The pathogenesis behind TTP is due to the deficiency of ADAMTS 13. ADAMTS13 is a metalloprotease which cleaves high molecular weight or ultralarge von Willebrand factor to smaller von Willebrand factor. The ultralarge von Willebrand factor is very thrombogenic, and its presence triggers the development of microthrombi in the microvascular circulation. The microvascular thrombi cause mechanical damage to the regular cell and the typical picture of TTP. The level of ADAMSTS 13 is usually lower in patients with TTP. But the level is not mandatory to make the diagnosis of TTP. This is because this test has limited availability, in the level three difference, and urgency to treat the patient before the results of the test is available. In classical HUS, the culprit is due to verotoxin that is present in the bloodstream of patients. This verotoxin caused disruption of the endothelia and creates a pro-thrombogenic environment. The diagnosis of both TTP or HUS is based on clinical features or criteria. Although classically TTP have five main clinical presentations. However, the presence of microangiopathic hemolytic anemia with thrombocytopenia without other explainable cause is the key to the diagnosis of TTP. Few guidelines also recommend a similar approach to the diagnosis of TTP. This is because when patients have all the clinical features, they are usually very sick, with a high mortality rate. Early intervention based on high clinical suspicion with supportive laboratory results will help with the diagnosis of TTP. It is important to investigate for possible etiology of TTP, as this has prognostic significance to plasma exchange and other conventional treatment. HUS usually presents with classical triad, however certain patients may have more extensive multiorgan disease, such as anteriocolitis, neurological complications, liver dysfunction, pancreatic and cardiac problems. In this rare situation, differentiations between TTP is difficult. This slide shows the typical blood film of patients with micro hemolytic anemia. These arrows show the classical cystocytes. These cells are fragments of red blood cell, due to mechanical damage when the red blood cell pass through microcirculation with microthrombi. Blood film usually will have increased young red blood cell or polychromic cell, and also thrombocytopenia. In contrast, the slide at the lower left shows a normal blood film. There is absence of fragmented cells and no thrombocytopenia. TTP or HUS is a clinical diagnosis. There are many other differential diagnoses to be considered. Shown here are the main differential diagnoses. DIVC, or Disseminated Intravascular Coagulation has similar findings on blood film, although with the last fragmented cells and may have raised white blood cell with toxic granulation in the neutrophils. Patients usually have underlying etiology for the development of the DIVC, such as infection. Evans syndrome is an autoimmune disease characterized by autoimmune hemolytical anemia, AHA, and immune thrombocytopenia, IPT. The main level three difference is that Evan’s syndrome has a positive direct glutination test. HELLP Syndrome occurs in pregnancy and is associated with the raising of enzyme. Malignant hypertension is an important differential not to be missed as the treatment is with good control of the blood pressure. Catastrophic antiphospholipid syndrome, APS, is a medical emergency and patients may have underlying SLE. Catastrophic APS causes multi-organ failure and the prognosis is generally poor. Investigation for TTP or HUS are mainly to identify the presence of microangiopathic hemolytic anemia, MAHA, thrombocytopenia, renal impairment and to rule out other possible differential diagnoses. Shown here are some of the important investigation that need to be done. We would also need to look for possible etiology of the TTP or HUS, such as autoimmune disease and infection. TTP is a fatal disease if not identified early with a high mortality rate of 80 to 90 percent. The widespread recognition of this disease with early initiation of plasma exchange have improved the survival significantly to about 70% to 80%. The plasma exchange is done with fresh frozen plasma, or FFP. Patients usually have transient drop in platelet count before further improvement in their status. TTP is a prothrombogenic condition and as the platelet improves, anti-platelet agent should be added. Other agents that can be used when patients show poor response are agents such as steroid, monoclonal a antibodies such as doximet and chemotherapy. We will need to identify possible underlying etiology for the TTP such as underlying autoimmune disease or retroviral infection. HUS is usually treated conservatively as patient have good recovery of their organ function. Occasionally, certain patients may require supportive treatment. In summary, TTP is a fatal, yet highly treatable disease with early recognition and intervention.

6 comments / Add your comment below

  1. Relevant information depicted !! its very helpful… last month i met my old school friend who was going through hard times , he was suffering from chronic ITP and then i suggested him about Planet Ayurveda's ITP care pack … now he is much better and healthier as comparison to last month when i saw him. There is still a ray of hope which will treat in better way..

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