Summary about Disease
Thrombotic microangiopathy (TMA) is a group of disorders characterized by microangiopathic hemolytic anemia (destruction of red blood cells), thrombocytopenia (low platelet count), and organ damage. The underlying cause involves widespread thrombosis (blood clot formation) in the small blood vessels (microvasculature) throughout the body. This leads to organ dysfunction and potential failure. There are multiple types of TMA, including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS).
Symptoms
Symptoms of TMA vary depending on the organs affected, but common signs include:
Fatigue and weakness: Due to anemia.
Purpura (bruising): Small, pinpoint-sized red or purple spots on the skin.
Pallor (pale skin): Due to anemia.
Jaundice (yellowing of the skin and eyes): Due to red blood cell breakdown.
Neurological symptoms: Confusion, headache, seizures, stroke, visual disturbances, coma.
Kidney problems: Decreased urination, blood in urine, swelling in legs and feet.
Fever: Can be present in some cases.
Abdominal pain, nausea, vomiting, diarrhea: Especially in HUS.
Causes
The causes of TMA are diverse and depend on the specific type:
TTP (Thrombotic Thrombocytopenic Purpura): Often caused by a deficiency or inhibition of the ADAMTS13 enzyme, which normally cleaves von Willebrand factor (vWF). This leads to the accumulation of ultra-large vWF multimers that promote platelet aggregation and microthrombi formation. This deficiency can be acquired (autoimmune) or inherited.
HUS (Hemolytic Uremic Syndrome):
Shiga toxin-producing E. coli (STEC-HUS): Most commonly caused by infection with E. coli O157:H7, which produces Shiga toxin that damages the endothelial cells lining blood vessels, particularly in the kidneys.
Atypical HUS (aHUS): Caused by genetic mutations affecting the complement system, a part of the immune system. These mutations lead to uncontrolled complement activation and damage to the endothelial cells.
Secondary TMAs: Can be triggered by medications (e.g., calcineurin inhibitors, chemotherapy drugs), autoimmune diseases (e.g., systemic lupus erythematosus), infections (e.g., HIV), pregnancy, cancer, and stem cell transplantation.
Medicine Used
Treatment depends on the specific type and severity of TMA:
TTP:
Plasma exchange (PEX): To remove antibodies against ADAMTS13 and replace the deficient enzyme.
Immunosuppressants: Corticosteroids (e.g., prednisone), rituximab (targets B cells that produce autoantibodies), caplacizumab (inhibits vWF-platelet interaction).
HUS:
STEC-HUS: Primarily supportive care, including hydration, blood transfusions, and dialysis if needed. Antibiotics are generally avoided as they may increase Shiga toxin release.
Atypical HUS: Eculizumab or ravulizumab (complement inhibitors that block the uncontrolled complement activation).
Supportive care: Blood transfusions, platelet transfusions (use with caution in TTP), dialysis for kidney failure, antihypertensive medications.
Is Communicable
TTP: Not communicable. It is primarily an autoimmune or genetic disorder.
HUS: STEC-HUS is communicable. It is caused by a bacterial infection that can be spread through contaminated food, water, or contact with infected individuals or animals. Atypical HUS is not communicable.
Precautions
Precautions depend on the type of TMA:
TTP: No specific precautions to prevent recurrence, but regular monitoring for relapse is necessary.
STEC-HUS:
Preventing infection: Thoroughly cook ground beef, wash fruits and vegetables, avoid unpasteurized milk and juices, wash hands frequently, especially after using the restroom or handling raw meat.
Avoiding spread: If infected, practice good hygiene to prevent spreading the bacteria to others.
Atypical HUS: No specific precautions to prevent the initial onset, as it's typically genetically determined, but management focuses on preventing complications and relapses with medication.
How long does an outbreak last?
The duration of a TMA outbreak varies depending on the type and promptness of treatment:
TTP: Without treatment, TTP can be rapidly fatal (days to weeks). With prompt plasma exchange and immunosuppression, remission is possible, but relapses can occur.
STEC-HUS: The acute phase of STEC-HUS typically lasts 1-2 weeks. Kidney damage can be permanent in some cases.
Atypical HUS: Atypical HUS is a chronic condition that requires long-term management with complement inhibitors to prevent relapses and organ damage.
Secondary TMAs: Varies based on the underlying cause and response to treatment.
How is it diagnosed?
Diagnosis involves a combination of clinical findings and laboratory tests:
Complete blood count (CBC): To detect anemia and thrombocytopenia.
Peripheral blood smear: To look for schistocytes (fragmented red blood cells).
Coagulation studies: To rule out other clotting disorders (e.g., disseminated intravascular coagulation).
ADAMTS13 activity level: To diagnose TTP (a level <10% is highly suggestive).
Shiga toxin testing: To diagnose STEC-HUS.
Complement studies: To evaluate for complement dysregulation in atypical HUS.
Renal function tests: To assess kidney damage.
Other tests: To rule out secondary causes of TMA (e.g., autoimmune workup, medication review, infection screening).
Genetic testing: to confirm atypical HUS
Timeline of Symptoms
The timeline of symptoms can vary, but a general progression is:
TTP: Symptoms can develop rapidly over days to weeks. Patients may initially experience fatigue, purpura, and fever, followed by more severe manifestations like neurological symptoms and kidney dysfunction.
STEC-HUS: Symptoms typically start with diarrheal illness (often bloody) 3-7 days after infection. After a few days, patients may develop signs of TMA, including pallor, fatigue, decreased urination, and neurological symptoms.
Atypical HUS: Can present acutely or insidiously. Acute episodes may resemble STEC-HUS, while chronic aHUS can lead to gradual kidney damage and other organ dysfunction.
Important Considerations
TMA is a medical emergency requiring prompt diagnosis and treatment.
Differentiation between TTP, STEC-HUS, and atypical HUS is crucial for appropriate management.
Treatment strategies vary depending on the underlying cause.
Long-term monitoring is often necessary to detect relapses and manage complications.
Consultation with hematologists, nephrologists, and other specialists is essential for optimal patient care.