A 16 year old child came in to the emergency department with history of easy bruising for one month and an episode,of seizure the day before admission. On further investigations, she was found to have severe anaemia and thrombocytopenia. She was diagnosed by Dr Marashi as a case of acquired thrombotic thrombocytopenic purpura.
The diagnosis was made within six hours of presentation, which is absolutely crucial in the case of TTP. The patient was started on plasma exchange and a decision was made to put her on the newly approved drug Caplacizumab. This made a huge difference in the outcome. The patient showed a rapid response and required only three sessions of plasma exchange. This rapid improvement was noted in both the clinical state of the patient as well as the laboratory parameters. This rapid improvement was important, as it avoided several additional sessions of plasma exchange and resulted in a lower risk of both acute and chronic complications of this serious disease. This also allowed early discharge from the hospital, without any complication. The drug was continued after discharge and is administered as a subcutaneous injection.
The successful outcome of this case is testament to the expertise of our physicians and how we work with the latest and the most innovative medical breakthrough to improve our patient outcomes.
Thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease caused by a deficiency of the metalloproteinase, ADAMTS13, often due to autoimmunity. This leads to the development of pathogenic multimers of von Willebrand factor (vWF), causing an inappropriate interaction between platelets and vWF, resulting microvascular occlusion. In this disease, tiny clots then form in the body that can cause major consequences as they can block blood vessels, which stops blood from being able to reach vital organs. This can compromise the functioning of thes organs such as your heart, brain, and kidneys and lead to fatal outcomes.
TTP is a medical emergency. It is almost always fatal if appropriate treatment is not initiated promptly. With appropriate treatment, survival rates of up to 90 percent are possible. Delay in diagnosis and in initiating appropriate therapy will significantly affect outcome negatively.
TTP is most often acquired, due to an autoantibody inhibitor, or can be hereditary, due to inherited mutations in ADAMTS13.
The majority of cases of immune-mediated TTP are associated with the presence of autoantibodies directed against the von Willebrand factor-cleaving protease, ADAMTS13, resulting in a severe (< 10% of normal activity) ADAMTS13 deficiency. A trigger, including physical stress (surgery), infections, drug intake or a pregnancy, may precipitate the disease.
Patients usually present with bruising, fatigue, other symptoms of anemia, transient neurological defects and in severe cases seizures and/or evidence of myocardial injury.
Diagnosing TTP and initiating treatment is urgent. Standard therapy is with plasma exchange (PEX), which should be initiated urgently. PEX may be needed daily usually for anything from 5-15 days or longer. This is a time consuming procedure associated with significant side effects and complications. Delay in achieving remission also increases the risks of acute and long-term complications of this disease. However with the advanced and breakthrough innovation, a new approved drug is Caplacizumab, has been shown to achieve remission faster. It also facilitates earlier termination of plasma exchange.
Diagnosing TTP usually requires multiple tests. There are tools used to assist in diagnosis. The PLASMIC score is on such tool. In this case, the girl had on a PLASMIC score of 6/7 which meant that she had a high probability of TTP.
Plasmic Score is calculated using findings readily available at presentation and has been devised to predict the likelihood of ADAMTS13 activity ≤10 percent (to help estimate the pretest probability and support the diagnosis of TTP) The score gives one point each for the following features (calculator 1):
- Platelet count <30,000/microL
- Hemolysis (defined by reticulocyte count >2.5 percent, undetectable haptoglobin, or indirect bilirubin >2 mg/dL)
- No active cancer
- No solid organ or stem cell transplant
- MCV <90 fL
- INR <1.5
- Creatinine <2.0 mg/dL
The higher the score, the greater the likelihood of TTP:
- 0 to 4 points – low probability of TTP.
- 5 points – intermediate probability of TTP.
- 6 to 7 points – high probability of TTP.
The treatment of TTP includes immunosuppression and B-cell depletion with corticosteroids, mycophenolate and rituximab. These therapies are to suppress the antibody directed against ADAMTS13 and allow the level of ADAMTS13 to rise and thus correct the deficiency. They also help in decreasing the risk of relapse when plasma exchange and Caplacizumab therapy is completed.
Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor, which is the point of interaction with the glycoprotein Ib-IX-V receptor on the platelet membrane. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, and is therefore target specific. The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation
Caplacizumab clearly improves critical patient-centered outcomes such as thromboembolic event rate, death rate, relapse rate, hospitalization/ICU time, days of TPE, and time to normalization of markers of end-organ ischemic damage.
Caplacizumab results in a more rapid resolution of TTP episodes as indicated by faster platelet-count normalization. Studies have indicated that caplacizumab immediately inhibits the pathophysiological mediator of microthrombosis leading to improvement in organ-damage markers as well as reducing the numbers of exacerbations.