TTP Flashcards
Lab features of TTP
Hemolysis + schistocytes + *severe thrombocytopenia + normal PT/PTT
Signs/symptoms of TTP
- Typically several days of **nonspecific symptoms, such as progressive weakness, fatigue, purpura, and gastrointestinal symptoms (eg, nausea, diarrhea).
- Some have minimal symptoms.
- Neuro: No neurologic symptoms (30%). Confusion, headache (30%). Severe neuro symptoms (30%).
General process for working up suspected TTP
CLINICAL
1) Calculate **PLASMIC score
https: //www.mdcalc.com/plasmic-score-ttp
2) Initiate therapy pending result, don’t wait for ADAMTS13
pathophysiology of acquired TTP
Autoantibody to protease ADAMTS13, which cleaves the high-molecular-weight multimers of von Willebrand factor (vWF). The decrease in ADAMTS13 activity leads to accumulation of clumps of ultra-large-molecular-weight vWF multimers, which bind to masses of platelets leading to microvascular occlusion and thrombocytopenia.
TTP prognosis
Almost always fatal if appropriate treatment is not initiated promptly;
other monoclonal antibody that can be used for TTP treatment and mechanism
caplacizumab (anti-von Willebrand factor (VWF) antibody)
cornerstone of therapy for TTP
Plasma exchange (PLEX)
how does plasma exchange treat TTP
PEX involves removal of the patient’s plasma by apheresis and replacement with donor plasma. In TTP, this is assumed to work by replacing ADAMTS13 and removing the autoantibodies that are inhibiting ADAMTS13 activity as well removing residual ultralarge von Willebrand factor (VWF) multimers.
why is rituximab used for TTP?
Rituximab is a chimeric monoclonal antibody directed against CD20 – kills B cells and reduced production of antibody VWF inhibitor
TTP diagnosis
Calculate PLASMIC score
https://www.mdcalc.com/plasmic-score-ttp
initiate therapy pending result, don’t wait for ADAMTS13
Treatment for TTP
daily plasmapheresis (PLEX) until platelet count recovers (may take 1-2 weeks)
methylprednisolone 1000 mg IV daily for 3 days
IF improving → switch to prednisone 1 mg/kg PO daily
IF no hep B → rituximab (dosed after PLEX) 375 mg/m2 IV qweek x 4 weeks
IF bleeding → platelet transfusion
2 major etiologies of TTP
1) autoimmunity (antibody mediated inhibition of ADAMTS13 enzyme)
2) inherited deficiency of ADAMTS13
Pathophys of TTP
*see MDAnderson slide
Inability to cleave VWF multimeres leads to adhesion and aggregation of platelets –> Platelets are consumed in the aggregation process and bind vWF –> platelet-vWF complexes form clots in small blood vessels –> clots cause shearing of red blood cells, resulting in their rupture and formation of schistocytes.
Classic pentad of TTP
MAHA thrombocytopenia renal failure neuro abnormalities fever
monoclonal ab that inhibits VWF-platelet interaction
caplacizumab
