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Thrombotic Thrombocytopenic Purpura
Thrombotic microangiopathy from reduced activity of ADAMTS13 (von Willebrand factor-cleaving protease)
- Acute or Insidious Onset of Clinical Pentad (though all elements of pentad are rarely seen in the same individual)
- Thrombocytopenia
- Often causes petechiae or purpura
- Oral, GI, GU bleeding less common, but can be severe
- Microangiopathic Hemolytic Anemia (MAHA)
- Neurological symptoms
- Ranges from headache to transient changes in mentation/behavior to seizures or coma
- Fever
- Most common symptom
- Usually low-grade (≥ 39°C suggests infection rather than TTP)
- Renal dysfunction
- Usually mild; ARF in < 10% of cases
- Oliguric ARF at presentation very uncommon
- Overall, thrombocytopenia in setting of MAHA is sufficient to suggest the diagnosis
- Thrombocytopenia
- Laboratory Features (can vary depending on timing of presentation):
- Thrombocytopenia:
- Usually severe; ½ of patients have platelet count <20,000mL
- MAHA:
- Anemia with increased reticulocyte count, decreased haptoglobin, increased direct bilirubin (may be mild elevation), increased LDH, negative DAT
- Schistocytes on peripheral smear
- Coagulation Factors:
- PT/aPTT typically normal
- ADAMTS-13 Activity:
- Often severely deficient (<5%), +/- presence of inhibitor
- Aids to confirm diagnosis (performed by few labs in country, slow turn-around time)
- Awaiting result should not delay initiation of therapy if TTP strongly suspected
- DDx:
- Hemolytic Uremic Syndrome
- DIC/Sepsis
- MAHA post-Solid Organ Transplantation/Stem Cell Transplant
- Often associated with tacrolimus/cyclosporine toxicity
- MAHA with metastatic adenocarcinoma, acute erythroleukemia
- Drug induced MAHA
- Clopidogrel: <2 weeks of use; milder thrombocytopenia, AKI common; ADAMTS13 activity >15%
- Quinine
- Cyclosporine/Tacrolimus
- Mitomycin C, Gemcytabine
- HELLP
- Malignant Hypertension
- Auto-Immune Disorders
- Evan’s Syndrome: Positive DAT; prominent spherocytes > schistocytes
- SLE with vasculitis: Palpable purpura, ANA+, low complement levels
- Scleroderma renal crisis
- Treatment
- If plasma exchange is not available: immediate transfusion of FFP (30 mL/kg) while en route to center that can offer therapeutic plasma exchange (TPE)
- Daily Therapeutic Plasma Exchange (TPE)
- Immediately contact service responsible for pheresis activities: at both UMC and Tulane, coordinated via Blood Bank
- Will require placement of Hemodialysis-type vascular access (e.g.: Trialysis, Quinton catheters)
- Should be placed ASAP
- Glucocorticoids
- Prednisone or equivalent, 1-2 mg/kg/day until remission achieved
- Should be dosed after exchange (TPE will remove steroid binding proteins)
- Transfusion Support:
- RBCs as needed
- Platelet transfusion generally contraindicated except in setting of life-threatening hemorrhage
- Duration of Treatment
- TPE/steroids until complete remission (normal neuro status, platelet count >150,000/mL, rising Hgb, normal LDH) for 2-3 days
- Then stop TPE and start steroid taper (though # of, or weaning of, TPE sessions following remission varies by center)
- Refractory/Relapsing TTP
- Treatment includes: Intensifying TPE, Immunosuppression (cyclophosphamide, rituximab), consider splenectomy
- Thrombocytopenia: