Vignette says a 35 year old female presents with a 3 day history of fatigue, headaches and confusion; She also reports small purple spots on her legs; On examination, she has pallor, petechiae on her legs, and mild jaundice; Vital signs show blood pressure of 130/80 mm of Hg, pulse rate of 98 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 92% in RA and temperature of 99.9 F; Examination shows pale bulbar conjunctiva and palms; Laboratory studies show hemoglobin of 8.0 mg/dL, platelet count of 30K, LDH of 600 U/L (normal range is 135-225 U/L), serum creatinine levels of 1.8 (normal range is 0.7-1.3 mg/dL), indirect bilirubin of 1.8 mg/dL (normal range is 0.2 to 0.8 mg/dL) and low haptoglobin levels; PBS shows schistocytes; Coombs test is negative; ADAMTS13 assay activity is decreased (i.e. <10% of ADAMTS13 activity; Diagnosis?
Diagnosis is Thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia
(MAHA) characterized by the pentad of fever, hemolytic anemia, thrombocytopenia, and
renal and neurologic dysfunction.
(MAHA) characterized by the pentad of fever, hemolytic anemia, thrombocytopenia, and
renal and neurologic dysfunction.
Pathophysiology:- Inhibition or deficiency of ADAMTS13 activity (a protease that cleaves von Willebrand factor); It leads to decreased degradation of large vWF multimers; persistence of large vWF multimers on the endothelial surface causes platelet adhesion, aggregation and subsequent thrombus formation.
Clinical features:-
1. MAHA
2. Thrombocytopenia
3. Acute renal failure
4. Altered mental status
5. Fever
1. MAHA
2. Thrombocytopenia
3. Acute renal failure
4. Altered mental status
5. Fever
Diagnosis:-
1. CBC shows decreased platelet count, decreased hemoglobin, increased reticulocyte count.
2. Coagulation profile shows normal PT and aPTT.
3. PBS analysis shows schistocytes (>2–3/hpf).
4. Increased LDH, increased indirect bilirubin, decreased haptoglobin, Coombs negative
hemolytic anemia.
5. Deranged RFT.
6. ADAMTS13 assay detects auto antibody against ADAMTS13.
7. ADAMTS13 assay activity is decreased (i.e. <10% of ADAMTS13 activity).
1. CBC shows decreased platelet count, decreased hemoglobin, increased reticulocyte count.
2. Coagulation profile shows normal PT and aPTT.
3. PBS analysis shows schistocytes (>2–3/hpf).
4. Increased LDH, increased indirect bilirubin, decreased haptoglobin, Coombs negative
hemolytic anemia.
5. Deranged RFT.
6. ADAMTS13 assay detects auto antibody against ADAMTS13.
7. ADAMTS13 assay activity is decreased (i.e. <10% of ADAMTS13 activity).
Treatment:-
1. Plasmapheresis and high dose steroids are the mainstay of therapy.
2. Rituximab (i.e. Anti-CD20 monoclonal antibody).
3. No platelet transfusions (may cause thrombus formation).
4. Splenectomy if refractory to plasmapheresis & steroids.
1. Plasmapheresis and high dose steroids are the mainstay of therapy.
2. Rituximab (i.e. Anti-CD20 monoclonal antibody).
3. No platelet transfusions (may cause thrombus formation).
4. Splenectomy if refractory to plasmapheresis & steroids.