Anemia and Thrombocytopenia

Shirley P. Levine, MD

Albert Einstein College of Medicine, Bronx, NY

Copyright of the American Society of Hematology, 2006. ISSN: 1931-6860.

This case was reviewed and updated in November 2011 by Dr. Howard Liebman and members of the Teaching Cases Subcommittee.

V. PATHOPHYSIOLOGY

The pathophysiology for TTP is under intensive study and may include both endothelial injury and intravascular platelet aggregation.

Endothelial Injury: There have been many observations in patients with TTP, which could support this mechanism. There are reports of anti-endothelial cell antibodies, increased endothelial cell apoptosis, decreased prostacyclin production, and increased endothelial cell thrombomodulin expression. However, none of these changes is found in all patients, or even in a majority of patients, with acute TTP. Recent studies regarding a related syndrome, hemolytic uremic syndrome (HUS), strongly suggest a mechanism of complement mediated endothelial injury due to either acquired or congenital defects in complement regulation cascade and complement inhibitory mechanisms. HUS patients have normal ADAMTS13 activity and the disease has a predilection for renal injury.

Intravascular Platelet Aggregation: Recent experimental data from two separate laboratories suggest that the main abnormality is in von Willebrand Factor homeostasis, which in turn is responsible for intravascular platelet aggregation. Microvascular platelet thrombi are found in the brain, heart, kidney, pancreas, adrenal glands, spleen, and elsewhere. The distribution of these thrombi is responsible for the clinical manifestations of TTP.

The Bone Marrow Biopsy in this patient did demonstrate intravascular hyaline thrombi suggestive of TTP.

Bone Marrow Biopsy Under Oil Immersion; Hematoxylin-eosin stain.

The bone marrow cellularity appears normal. There is a hyaline thrombus in a bone marrow vessel, which is compatible with a diagnosis of TTP. When these hyaline thrombi are analyzed in TTP, they are found to contain von Willebrand Factor (vWF) and platelet antigens, and only small amounts of fibrin. This is in contrast to any microvascular thrombi seen in DIC. In DIC, the thrombi contain large amounts of fibrin.

To review evidence for abnormal von Willebrand Factor homeostasis, click here


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