ASH Image Bank (2001); doi:10.1182/ashimagebank-2001-100174
Copyright © 2001 by the American Society of Hematology.
Thrombotic Thrombocytopenic Purpura
John Lazarchick, MD
Medical University of South Carolina
View larger version (149K):
[in this window]
[in a new window]
|
Figure 1. Peripheral smear showing microangiopathic hemolytic features with numerous RBC fragments (helmet cells/schistocytes). Marked thrombocytopenia is evident.
|
|
View larger version (122K):
[in this window]
[in a new window]
|
Figure 2. Peripheral smear showing RBC fragmentation consistent with a microangiopathic hemolytic process.
|
|
View larger version (171K):
[in this window]
[in a new window]
|
Figure 5. Bone marrow biopsy showing megakaryocytic hyperplasia with mature and immature forms present.
|
|
View larger version (57K):
[in this window]
[in a new window]
|
Figure 8. von Willebrand factor protein multimer analysis on agarose gel electrophoresis. Lane 1: Normal plasma. Lane 2: Patient plasma when symptomatic. Multimer pattern is similar to the control plasma. Lane 3: Patient plasma after response to pheresis. Note the presence of ultra-large high molecular weight multimers.
|
|
 |
Clinical Summary
|
|---|
A 56-year-old woman was transferred from an outside hospital in an obtunded state. Family members stated she had been at a church social event and began to act "funny." She seemed disoriented and had difficulty with speech. Over the course of several hours, her condition progressed and her family took her to the local emergency department. She had been in good health prior to this time with no history of hypertension or diabetes. She was not taking any medications. No one else in the family was ill.
Physical examination: She was obtunded and not easily arousable. No localizing neurologic deficit was noted but her reflexes were suppressed. Diffuse petechiae were present on her upper extremities and multiple ecchymotic areas on her buttocks and lower extremities. Her sclera were icteric. Exam of her fundi, chest, and abdomen were unrevealing.
Lab: Hemoglobin (Hgb) 7.2 g/dL; white blood cells (WBC) 16,400; platelets 7,000/uL; reticulocytes 12%; creatinine 1.4mg/dL.
Sex
Female
Age
56
Ethnicity
n/a
|
Diagnosis
|
|---|
Disseminated intravacular coagulation, Malignant hypertension, Metastatic carcinoma, Pregnancy-related hemostatic disorders
|
Discussion
|
|---|
Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is a hemorrhagic disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia, and accompanied by fever, renal dysfunction, and vacillating neurologic signs and symptoms. Thrombi consisting primarily of platelets (hyaline thrombi) can be demonstrated in terminal arterioles and capillaries. Current classification depends on the underlying etiology and includes: HUS (associated with E coli 0157.H) and adult syndromes of idiopathic TTP and those associated with other conditions, including drug-induced (ticlopidene, cyclosporin), following bone marrow transplantation, metastatic carcinoma, pregnancy-related disorders (preeclampsia, HELLP syndrome), and autoimmune disorders (systemic lupus erythematosus, anti-phospholipid antibody syndrome). While the etiology of this disorder is unknown, spontaneous binding of ultra-large/large high molecular weight von Willebrand factor (VWF) multimers to unactivated platelets is thought to be central to the underlying pathophysiology. Under normal hemostatic conditions, these multimers, once secreted from endothelial cells, undergo proteolytic cleavage by a metalloprotease (VWF cleaving enzyme) and thus the multimer size in circulation and in the subendothelial matrix is rigidly controlled. It is now realized that in many patients who develop TTP this protease is either absent or an autoantibody is present which inhibits its activity. This results in the presence of ultra-large VWF multimers in circulation, which are capable of spontaneously binding to platelet membrane glycoprotein Ib/IX complex on unstimulated platelets leading to thrombi formation and the resultant clinical syndrome. In HUS and other cases of this syndrome, metalloprotease activity is normal. The hemorrhagic diathesis associated with this disorder results in mucocutaneous bleeding which can be severe. Laboratory studies include marked thrombocytopenia with an increased mean platelet volume (MPV), red blood cell (RBC) fragments on the peripheral smear, elevated serum bilirubin (predominantly the indirect fraction), decreased or absent serum haptoglobin, and marked elevation of lactate dehydrogenase (LDH). Aggressive plasmapheresis is the mainstay of therapy of this disorder. Daily plasma exchange of at least one plasma volume should be promptly initiated and continued until the platelet count and LDH normalize and neurologic symptoms have resolved. Replacement fluid can be either fresh frozen plasma or cryoprecipitate supernatant plasma. Exacerbations during the course of therapy with episodic drops in platelet count and rising LDH can be seen in 20% to 40% of cases. Survival is now 80% but recurrences are seen in one-third of patients.
|
Differential Diagnosis
|
|---|
Disseminated intravacular coagulation, Malignant hypertension, Metastatic carcinoma, Pregnancy-related hemostatic disorders
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| Related Image Bank Image Sets | |  |
-
Chronic Lymphocytic Leukemia: Thrombocytopenia
- John Lazarchick
ASH Image Bank 2001 2001: 100175.
[Full Text]
-
Idiopathic Thrombocytopenic Purpura
- John Lazarchick
ASH Image Bank 2001 2001: 100177.
[Full Text]
-
Megakaryocyte
- Peter Maslak
ASH Image Bank 2002 2002: 100468.
[Full Text]
-
Essential Thrombocythemia
- Peter Maslak
ASH Image Bank 2003 2003: 100634.
[Full Text]
-
Platelet Formation
- Peter Maslak
ASH Image Bank 2003 2003: 100873.
[Full Text]
-
Giant Platelet
- Peter Maslak
ASH Image Bank 2004 2004: 100950.
[Full Text]
-
Giant Platelet
- Peter Maslak
ASH Image Bank 2004 2004: 101140.
[Full Text]
-
Von Willebrand Disease - Type 2b
- John Lazarchick
ASH Image Bank 2004 2004: 101146.
[Full Text]
-
Immune Thrombocytopenic Purpura
- Peter Maslak
ASH Image Bank 2004 2004: 101214.
[Full Text]
-
Platelet-Forming Megakaryocyte
- Peter Maslak
ASH Image Bank 2004 2004: 101228.
[Full Text]
-
Pseudoschistocytosis secondary to cryoglobulinemia
- Rabih Faheed, Brian Barnett, and Marc J. Kahn
ASH Image Bank 2007 2007: 700026.
[Full Text]
| Related ASH Education Book Articles | |  |
-
Platelets: Thrombotic Thrombocytopenic Purpura
- James N. George, J. Evan Sadler, and Bernhard Lämmle
Hematology 2002 2002: 315-334.
[Abstract]
[Full Text]
-
Recent Advances in Thrombotic Thrombocytopenic Purpura
- J. Evan Sadler, Joel L. Moake, Toshiyuki Miyata, and James N. George
Hematology 2004 2004: 407-423.
[Abstract]
[Full Text]
| Related ASH-SAP Chapter: |
 |
-
Chapter 15: Hemostasis and Thrombosis
Copyright © 2001 by the American Society of Hematology.
TOP
Clinical Summary
Diagnosis
