General principle:
Acute presentation of severe to moderate thrombocytopenia. May present with fever, neurologic signs or symptoms and renal abnormalities. The complete pentad of signs/symptoms (i.e. thrombocytopenia, microangiopathic hemolytic anemia, fever and neurologic and renal abnormalities) is present in fewer than 25% of cases.
Etiology: 1. Autoimmune - may be HIV associated
2. Congenital
Pathophysiology
1. Deficiency of von Willibrand factor-cleaving enzyme (ADAMTS 13) results in persistence of large multimeric forms and increased platelet adhesion.
a. autoimmune (i.e. idiopathic) TTP: autoantibody forms against ADAMTS 13
b. congenital TTP: Familial decrease in production of functional ADAMTS 13
2. Formation of platelet thrombi in microvasculature leads to tissue ischaemia and end organ disease
3. Intravascular hemolysis by increased shearing forces
Diagnosis
1. Laboratory
a. thrombocytopenia
b. red cell fragnments on peripheral blood film (shistocytes)
c. elevated LDH
d. Indirect bilirubin may be elevated
e. hemostasis parameters otherwise normal
f. creatinine may be increased, hematuria may be present
g. Usefullness of ADAMTS 13 level and antibody for diagnosis controversial
Treatment:
-Medical emergency: more than 90% mortality without treatment
-Institute immediate plasma exchange; replacement fluid must be plasma
-continue daily plasma exchange until LDH and platelet count have normalized for 2-3 days, then begin to taper frequently of plasma exchange
-transfuse FFP (4-6 units in an adult) if plasma exchange delayed
-corticosteroids - role unclear
-Patients with renal failure - hemodialysis
-refractory cases -splenectomy, vincristine, rituximab, immunosuppression
Prognosis
1. 90% mortality without rapid institution of therapy
2. Relapses after reduction/discontinuation of plasma exchange occur in a minority of patients
Hemolytic Uremic Syndrome
Pathophysiology:
1. deposition of platelet thrombi in small and medium sized vessels
2. no deficiency of ADAMTs 13
3. Especially in children, antecedent gastrointestinal illness and exposure to bacterial toxins may precede illness ("endemic HUS")
Treatment
1. Primarily supportive e.g. dialysis
2. Plasma exchange of value in some patients
3. Most cases resolve with supportive care
Acute presentation of severe to moderate thrombocytopenia. May present with fever, neurologic signs or symptoms and renal abnormalities. The complete pentad of signs/symptoms (i.e. thrombocytopenia, microangiopathic hemolytic anemia, fever and neurologic and renal abnormalities) is present in fewer than 25% of cases.
Etiology: 1. Autoimmune - may be HIV associated
2. Congenital
Pathophysiology
1. Deficiency of von Willibrand factor-cleaving enzyme (ADAMTS 13) results in persistence of large multimeric forms and increased platelet adhesion.
a. autoimmune (i.e. idiopathic) TTP: autoantibody forms against ADAMTS 13
b. congenital TTP: Familial decrease in production of functional ADAMTS 13
2. Formation of platelet thrombi in microvasculature leads to tissue ischaemia and end organ disease
3. Intravascular hemolysis by increased shearing forces
Diagnosis
1. Laboratory
a. thrombocytopenia
b. red cell fragnments on peripheral blood film (shistocytes)
c. elevated LDH
d. Indirect bilirubin may be elevated
e. hemostasis parameters otherwise normal
f. creatinine may be increased, hematuria may be present
g. Usefullness of ADAMTS 13 level and antibody for diagnosis controversial
Treatment:
-Medical emergency: more than 90% mortality without treatment
-Institute immediate plasma exchange; replacement fluid must be plasma
-continue daily plasma exchange until LDH and platelet count have normalized for 2-3 days, then begin to taper frequently of plasma exchange
-transfuse FFP (4-6 units in an adult) if plasma exchange delayed
-corticosteroids - role unclear
-Patients with renal failure - hemodialysis
-refractory cases -splenectomy, vincristine, rituximab, immunosuppression
Prognosis
1. 90% mortality without rapid institution of therapy
2. Relapses after reduction/discontinuation of plasma exchange occur in a minority of patients
Hemolytic Uremic Syndrome
Pathophysiology:
1. deposition of platelet thrombi in small and medium sized vessels
2. no deficiency of ADAMTs 13
3. Especially in children, antecedent gastrointestinal illness and exposure to bacterial toxins may precede illness ("endemic HUS")
Treatment
1. Primarily supportive e.g. dialysis
2. Plasma exchange of value in some patients
3. Most cases resolve with supportive care
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