Pathogenesis In A Patient With Thrombotic Thrombocytopenic Purpura

A 38-year-old woman presents with a 3-day history of fever and confusion. She was previously healthy and is taking no medications. She has not had diarrhea or rectal bleeding. She has a temperature of 38°C (100.4°F) and a blood pressure of 145/85. Splenomegaly is absent. She has no petechiae but does have evidence of early digital gangrene of the right second finger. Except for confusion the neurological examination is normal. Her laboratory studies reveal the following:
Hemoglobin: 8.7
Platelet count: 25,000
Peripheral smear: numerous fragmented RBCs, few platelets
LDH 562 (normal <180)
Creatinine: 2.7
Liver enzymes: normal
Prothrombin time/PTT/fibrinogen level: normal

What is the most likely pathogenesis of her condition?

A. Disseminated intravascular coagulation
B. Antiplatelet antibodies
C. Failure to cleave von Willebrand factor multimers
D. Verotoxin-induced endothelial damage
E. Cirrhosis with sequestration of erythrocytes and platelets in the spleen

Answer And Discussion:

The answer is C

This patient has thrombotic thrombocytopenic purpura (TTP). TTP is an acute life-threatening disorder that is characterized by the pentad of

1. microangiopathic hemolytic anemia,
2. nonimmune thrombocytopenia, 
3. fever, 
4. renal insufficiency, and 
5. CNS involvement (confusion or multifocal encephalopathy). 

Not all patients have the full pentad; the essential features are the red blood cell fragmentation (schistocytes andhelmet cells) and the thrombocytopenia. TTP may be triggered by endothelial damage and is associated with deficiency of a plasma protein (ADAMTS 13) that breaks down multimers of von Willebrand factor. Plasma exchange (with the infusion of fresh frozen plasma to provide the missing ADAMTS 13 protein) can be lifesaving.

The hemolytic uremic syndrome (often associated with verotoxin producing strains of E coli O157:H7) is similar but is usually not accompanied by CNS changes. The renal failure is usually more severe in HUS.

Disseminated intravascular coagulation associated with sepsis can resemble TTP, but the coagulation pathway is usually activated in DIC. In TTP the prothrombin time, PTT, and fibrinogen level are normal.

Antiplatelet antibodies are associated with idiopathic thrombocytopenic purpura (ITP), but this patient has multiple abnormalities, not just thrombocytopenia. Hypersplenism can cause thrombocytopenia but rarely with a platelet count of below 50,000; it is not associated with red cell fragmentation.