### 날짜 : 2024-01-20 18:08 ### 주제 : Thrombotic thrombocytopenic purpura (TTP) #medicine #hematology #공부 ---- # Thrombotic thrombocytopenic purpura (TTP) Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially life-threatening medical condition characterized by abnormal blood clot formation throughout the body, which leads to a decrease in platelet count (thrombocytopenia), red blood cell destruction (hemolytic anemia), and organ damage. TTP is considered a medical emergency and requires prompt diagnosis and treatment. Here are key features and details about TTP: 1. **Pathophysiology:** TTP is primarily caused by a deficiency or dysfunction of a protein called ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). ADAMTS13 is responsible for breaking down von Willebrand factor (vWF), a protein that helps with platelet adhesion and clot formation. In TTP, a deficiency of ADAMTS13 leads to the accumulation of unusually large vWF multimers in the blood, which causes the formation of microthrombi (small blood clots) throughout the body's small blood vessels, particularly in the brain, heart, kidneys, and other organs. 2. **Symptoms:** TTP is characterized by a pentad of clinical features, although not all five symptoms need to be present for a diagnosis: - Thrombocytopenia: A significant decrease in platelet count, leading to a higher risk of bleeding. - Microangiopathic hemolytic anemia: The presence of fragmented red blood cells due to mechanical damage as they pass through the microthrombi. - Neurological symptoms: This can include confusion, seizures, and even coma due to brain involvement. - Kidney dysfunction: Resulting in decreased urine output and potential kidney failure. - Fever and fatigue: General malaise may also be present. 3. **Causes:** TTP can occur spontaneously (idiopathic TTP) or be triggered by various factors, including infections, medications, autoimmune diseases, pregnancy, and bone marrow or stem cell transplants. Some cases of TTP are associated with an acquired autoantibody against ADAMTS13. 4. **Diagnosis:** Diagnosing TTP involves a combination of clinical assessment, blood tests (including a complete blood count, peripheral blood smear, measurement of ADAMTS13 activity, and assessment of red blood cell fragmentation), and sometimes a biopsy of affected tissues. 5. **Treatment:** TTP is a medical emergency, and prompt treatment is crucial. Treatment typically includes: - Plasma exchange (plasmapheresis): This procedure removes the patient's plasma, which contains the abnormal factors causing the clotting, and replaces it with fresh frozen plasma or donor plasma that contains functional ADAMTS13. - Corticosteroids: These anti-inflammatory medications are often used in conjunction with plasma exchange. - Immunosuppressive drugs: In cases where TTP is associated with autoimmune antibodies, medications like rituximab may be used. 6. **Prognosis:** With early and appropriate treatment, many individuals with TTP can recover. However, without timely intervention, TTP can lead to serious complications, including organ damage and death. TTP is a complex and potentially life-threatening condition that requires close monitoring and ongoing management even after initial treatment. Long-term follow-up care may be necessary to prevent recurrences and address any lingering complications. Patients diagnosed with TTP should work closely with a hematologist and other healthcare professionals experienced in managing this condition. # Case 1 **Patient Profile:** - Name: Jane - Age: 35 - Gender: Female - Medical History: No significant prior medical conditions **Presenting Symptoms:** Jane is admitted to the emergency department with the following symptoms: 1. **Fatigue and Weakness:** Jane has been feeling unusually tired for the past week, which she initially attributed to work stress and lack of sleep. 2. **Bruising and Petechiae:** She has noticed scattered small bruises on her arms and legs over the past few days. These bruises seemed to appear spontaneously, even without any significant injuries. Jane also has numerous tiny red spots on her skin called petechiae, which look like a rash but do not disappear when pressed. 3. **Fever and Headache:** Jane developed a low-grade fever (around 100.4°F or 38°C) and a persistent headache over the past two days. She describes the headache as severe and continuous, which is unusual for her. 4. **Neurological Symptoms:** Jane's family members have noticed changes in her behavior. She appears confused at times, forgetful, and disoriented. She has also experienced a brief episode of seizure-like activity. 5. **Kidney Dysfunction:** Jane has had a decrease in urine output and dark-colored urine over the past 24 hours. **Physical Examination Findings:** - On examination, Jane's skin reveals widespread petechiae and ecchymosis (larger bruises) on her extremities. - There are no obvious signs of external bleeding. - Blood pressure: Elevated (160/90 mm Hg). - Heart rate: Elevated (110 beats per minute). - Neurological examination shows mild confusion and agitation. **Diagnostic Tests:** - A complete blood count (CBC) reveals severe thrombocytopenia (platelet count <10,000/μL). - Peripheral blood smear shows the presence of fragmented red blood cells (schistocytes), indicative of microangiopathic hemolytic anemia. - Blood chemistry shows elevated serum creatinine and reduced urine output, suggesting kidney dysfunction. - ADAMTS13 activity testing reveals severely decreased activity (<10%), confirming the diagnosis of TTP. **Diagnosis:** Based on the clinical presentation and diagnostic findings, Jane is diagnosed with Thrombotic Thrombocytopenic Purpura (TTP). **Treatment:** Jane is immediately started on treatment, which includes: - Plasma exchange (plasmapheresis) to remove the abnormal factors causing the clotting and replace them with fresh frozen plasma. - High-dose corticosteroids to suppress the immune response. - Supportive care, including anticonvulsant medications to manage seizures and hydration to support kidney function. **Prognosis:** With prompt treatment, Jane's condition stabilizes over the next few days. Her platelet count gradually increases, and her neurological symptoms improve. She continues to receive plasma exchange therapy and is closely monitored. **Follow-up:** Jane is discharged from the hospital after several weeks of treatment, but her care is ongoing. She will need regular follow-up visits with a hematologist to monitor her condition and adjust treatment as needed to prevent recurrences. Education on potential triggers and symptoms of relapse is provided to Jane to help her manage her condition effectively.